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  • 003), earlier return to work times (MD, - 7.25 days; 95% CI, - 14.31 to - 0.19; P = 0.04), higher transient nerve injury rates (OR, 4.87; 95% CI, 1.37 to 17.25; P = 0.01), and a lower incidence of scar-related complications (OR, 0.20; 95% CI, 0.07 to 0.59; P = 0.004). The permanent nerve injury showed no significant differences between the two methods (OR, 1.93; 95% CI, 0.58 to 6.40; P = 0.28). CONCLUSIONS Overall, evidence from randomized controlled trials indicates that ECTR results in better recovery of daily life functions compared to OCTR, as revealed by higher satisfaction rates, greater key pinch strengths, earlier return to work times, and fewer scar-related complications. Our findings suggest that patients with CTS can be effectively managed with ECTR.OBJECTIVE This study was aimed to roughly describe individual Trans Fatty Acids (TFAs) intake and the percentage of energy intake(E%), and identify major food sources in the Chinese population, taking gender, age, and regional distribution into the consideration, as well as examining temporal changes over the course of 20 years. METHOD This multi-center study, covering nine provinces among populations aged ≥ 3 in China, was conducted to collect food consumption information from 1991 to 2011. A classical assessment method was used to estimate the level of dietary TFA intake. RESULTS Over the 20-year period, the intake of TFAs in Chinese populations had increased, but remained at a relatively lower level (from 0.25 g/d(0.11% for E%) to 0.53 g/d(0.24% for E%)) compared with that of other countries and the World Health Organization (WHO) recommended level. Collectively, males and participants aged 19-60 generally consumed more TFA-containing foods. People in eastern regions consumed more TFAs and had a higher E% than those in western area. Industrial sources of TFAs, especially vegetable oil, ranked as the principal food sources of TFAs in the Chinese population. Natural sources of TFAs have gradually increased in proportion among children and adolescents. CONCLUSIONS TFA intake and the E% are commonly under the recommended level in the general population in China. Presently, restriction of vegetable oil could be a crucial method to reduce TFA intake. It would be critical to facilitate and promote public health that food recommendations might be based on the dietary preferences for population separated by different ages and regions.BACKGROUND Maternal depression can influence the early activity of a mother reading stories to a young child, as depressed mothers are less likely to read to their children. Here, maternal depression association to neurobiological circuitry of narrative comprehension, visualization, and executive functions during stories listening was examined in 21 4-year-old girls and their mothers. Maternal depression scores were collected from the mothers, and functional MRI during stories listening was collected from the children. RESULTS Increased maternal depression was related to decreased functional connectivity between visualization and auditory regions and increased connectivity between the right visual cortex and dorsolateral prefrontal cortex in the children. CONCLUSIONS This study highlights the need to monitor maternal depression and provide interventions to ensure positive linguistic outcomes in children.There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course "Biomarkers in neurodegenerative diseases". In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis.BACKGROUND Diversified etiology of lower respiratory tract infection renders diagnosis challenging. The mainstay microbial culture is time-consuming and constrained by variable growth requirements. In this study, we explored the use of Nanopore sequencing as a supplementary tool to alleviate this diagnostic bottleneck. METHODS We developed a targeted Nanopore method based on amplification of bacterial 16S rRNA gene and fungal internal transcribed spacer region. https://www.selleckchem.com/products/oltipraz.html The performance was compared with routine infectious disease workups on 43 respiratory specimens. RESULTS Nanopore successfully identified majority of microbes (47/54, 87.04%) and 7 possible pathogens not detected by routine workups, which were attributable to the content of microbiological investigations (n = 5) and negative culture (n = 2). The average sequencing time for first target reads was 7 min (1-43 min) plus 5 h of pre-sequencing preparation. CONCLUSIONS The Nanopore method described here was rapid, economical and hypothesis-free, which might provide valuable hints to further microbiological follow-up for opportunistic pathogens missed or not detectable by conventional tests.BACKGROUND In Childhood-Onset Systemic Lupus Erythematosus (cSLE), poor medication adherence rates are very high. Interventions targeting this problem in cSLE are limited thus effective interventions are needed. The objective of this study is to examine the feasibility and acceptability an intervention (automated digital reminders + personalized prescribed treatment plan (pPTP)) to improve medication adherence in young adults with cSLE over 3 months. METHOD This is a proof-of-concept randomized controlled study. All participants received SimpleMed+ pillboxes that track adherence. The treatment group received a pPTP, and in month 2, preselected digital reminders for missed doses. Reminders were discontinued after 30 days and adherence data collected. Data analysis was done using t-tests. RESULTS Twenty-one participants were approached and nineteen consented to participate, yielding a recruitment rate of 86%. Participants were on average 20.5 years, mostly black (58%) and female (84%). Of the nineteen consented, eleven were randomized to control (57%) and eight to treatment (42%) groups respectively.
    003), earlier return to work times (MD, - 7.25 days; 95% CI, - 14.31 to - 0.19; P = 0.04), higher transient nerve injury rates (OR, 4.87; 95% CI, 1.37 to 17.25; P = 0.01), and a lower incidence of scar-related complications (OR, 0.20; 95% CI, 0.07 to 0.59; P = 0.004). The permanent nerve injury showed no significant differences between the two methods (OR, 1.93; 95% CI, 0.58 to 6.40; P = 0.28). CONCLUSIONS Overall, evidence from randomized controlled trials indicates that ECTR results in better recovery of daily life functions compared to OCTR, as revealed by higher satisfaction rates, greater key pinch strengths, earlier return to work times, and fewer scar-related complications. Our findings suggest that patients with CTS can be effectively managed with ECTR.OBJECTIVE This study was aimed to roughly describe individual Trans Fatty Acids (TFAs) intake and the percentage of energy intake(E%), and identify major food sources in the Chinese population, taking gender, age, and regional distribution into the consideration, as well as examining temporal changes over the course of 20 years. METHOD This multi-center study, covering nine provinces among populations aged ≥ 3 in China, was conducted to collect food consumption information from 1991 to 2011. A classical assessment method was used to estimate the level of dietary TFA intake. RESULTS Over the 20-year period, the intake of TFAs in Chinese populations had increased, but remained at a relatively lower level (from 0.25 g/d(0.11% for E%) to 0.53 g/d(0.24% for E%)) compared with that of other countries and the World Health Organization (WHO) recommended level. Collectively, males and participants aged 19-60 generally consumed more TFA-containing foods. People in eastern regions consumed more TFAs and had a higher E% than those in western area. Industrial sources of TFAs, especially vegetable oil, ranked as the principal food sources of TFAs in the Chinese population. Natural sources of TFAs have gradually increased in proportion among children and adolescents. CONCLUSIONS TFA intake and the E% are commonly under the recommended level in the general population in China. Presently, restriction of vegetable oil could be a crucial method to reduce TFA intake. It would be critical to facilitate and promote public health that food recommendations might be based on the dietary preferences for population separated by different ages and regions.BACKGROUND Maternal depression can influence the early activity of a mother reading stories to a young child, as depressed mothers are less likely to read to their children. Here, maternal depression association to neurobiological circuitry of narrative comprehension, visualization, and executive functions during stories listening was examined in 21 4-year-old girls and their mothers. Maternal depression scores were collected from the mothers, and functional MRI during stories listening was collected from the children. RESULTS Increased maternal depression was related to decreased functional connectivity between visualization and auditory regions and increased connectivity between the right visual cortex and dorsolateral prefrontal cortex in the children. CONCLUSIONS This study highlights the need to monitor maternal depression and provide interventions to ensure positive linguistic outcomes in children.There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course "Biomarkers in neurodegenerative diseases". In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis.BACKGROUND Diversified etiology of lower respiratory tract infection renders diagnosis challenging. The mainstay microbial culture is time-consuming and constrained by variable growth requirements. In this study, we explored the use of Nanopore sequencing as a supplementary tool to alleviate this diagnostic bottleneck. METHODS We developed a targeted Nanopore method based on amplification of bacterial 16S rRNA gene and fungal internal transcribed spacer region. https://www.selleckchem.com/products/oltipraz.html The performance was compared with routine infectious disease workups on 43 respiratory specimens. RESULTS Nanopore successfully identified majority of microbes (47/54, 87.04%) and 7 possible pathogens not detected by routine workups, which were attributable to the content of microbiological investigations (n = 5) and negative culture (n = 2). The average sequencing time for first target reads was 7 min (1-43 min) plus 5 h of pre-sequencing preparation. CONCLUSIONS The Nanopore method described here was rapid, economical and hypothesis-free, which might provide valuable hints to further microbiological follow-up for opportunistic pathogens missed or not detectable by conventional tests.BACKGROUND In Childhood-Onset Systemic Lupus Erythematosus (cSLE), poor medication adherence rates are very high. Interventions targeting this problem in cSLE are limited thus effective interventions are needed. The objective of this study is to examine the feasibility and acceptability an intervention (automated digital reminders + personalized prescribed treatment plan (pPTP)) to improve medication adherence in young adults with cSLE over 3 months. METHOD This is a proof-of-concept randomized controlled study. All participants received SimpleMed+ pillboxes that track adherence. The treatment group received a pPTP, and in month 2, preselected digital reminders for missed doses. Reminders were discontinued after 30 days and adherence data collected. Data analysis was done using t-tests. RESULTS Twenty-one participants were approached and nineteen consented to participate, yielding a recruitment rate of 86%. Participants were on average 20.5 years, mostly black (58%) and female (84%). Of the nineteen consented, eleven were randomized to control (57%) and eight to treatment (42%) groups respectively.
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  • ations on metastatic pattern, metastasis-free survival, and overall survival. © RSNA, 2020 See also the editorial by Choyke in this issue.Background The recently described "macrotrabecular-massive" (MTM) histologic subtype of hepatocellular carcinoma (HCC) (MTM-HCC) represents an aggressive form of HCC and is associated with poor survival. Purpose To investigate whether preoperative MRI can help identify MTM-HCCs in patients with HCC. Materials and Methods This retrospective study included patients with HCC treated with surgical resection between January 2008 and February 2018 and who underwent preoperative multiphase contrast material-enhanced MRI. Least absolute shrinkage and selection operator (LASSO)-penalized and multivariable logistic regression analyses were performed to identify clinical, biologic, and imaging features associated with the MTM-HCC subtype. Early recurrence (within 2 years) and overall recurrence were evaluated by using Kaplan-Meier analysis. Multivariable Cox regression analysis was performed to determine predictors of early and overall recurrence. Results One hundred fifty-two patients (median age, 64 years; interquartirecurrence. Conclusion At multiphase contrast-enhanced MRI, substantial necrosis helped identify macrotrabecular-massive hepatocellular carcinoma subtype with high specificity. © RSNA, 2020.Background Higher peak enhancement and washout component values measured on preoperative breast MRI scans with computer-aided diagnosis (***) are presumed to be associated with worse recurrence-free survival. Purpose To investigate whether ***-extracted kinetic features of breast cancer and the heterogeneity of these features at preoperative MRI are associated with distant metastasis-free survival in women with invasive breast cancer. Materials and Methods Consecutive women with newly diagnosed invasive breast cancer who underwent preoperative MRI were retrospectively evaluated between 2011 and 2012. https://www.selleckchem.com/products/tasin-30.html A commercially available *** system was used to extract the peak enhancement and delayed enhancement profiles of each breast cancer case from preoperative MRI data. The kinetic heterogeneity of these features (a measure of heterogeneity in the proportions of tumor pixels with delayed washout, plateau, and persistent components within a tumor) was calculated to evaluate intratumoral heterogeneity. Cox proportional Higher values of kinetic heterogeneity and peak enhancement as determined with computer-aided diagnosis of preoperative MRI were associated with worse distant metastasis-free survival in women with invasive breast cancer. © RSNA, 2020 See also the editorial by El Khouli and Jacobs in this issue.Aim To assess the potential of human induced pluripotent stem cell-derived smooth muscle cells (hiPSC-SMC) to accelerate diabetic wound healing. Methods hiPSC-SMC were embedded in 3D collagen scaffolds and cultured in vitro for 72 h; scaffolds were then applied to diabetic, nude mouse, splinted **** wounds to assess in vivo healing. Cultured medium after scaffold incubation was collected and analyzed for expression of pro-angiogenic cytokines. Results hiPSC-SMC secrete increased concentration of pro-angiogenic cytokines, compared with murine adipose derived stem cells. Delivery of hiPSC-SMC-containing collagen scaffolds accelerates diabetic wound healing and is associated with an increased number of total and M2 type macrophages. Conclusion hiPSC-SMC promote angiogenesis and accelerate diabetic wound healing, making them a promising new candidate for treatment of diabetic wounds.The unavoidable glycation reaction is the major cause of diabetes and metabolic disorders. The glycation reaction is enhanced in case when the glycating agent is reactive carbonyl species (RCS) like, methylglyoxal (MG). The impact of RCS may result into the diabetes mellitus and its secondary complications along-with its role in cancers too. This reaction can be discontinued by using natural product inhibitors or by chemically synthesized drugs, like aminoguanidine (AG). However, AG is reported to be nephrotoxic (toxic to kidneys) at a concentration of 10 mM or more and has therefore serious health concerns. In the present study, bioconjugation of AG was done with the gold nanoparticles (Gnps) to mitigate its toxic effect and upsurge the efficacy of AG on RCS induced glycation. The AG-Gnps formed waas characterized by UV-Vis. spectroscopy and it reveals a peak at 529 nm corresponding to AG-gold nanoparticles. The particle size of the AG-Gnp was found to be 12 nm in TEM while in DLS it was found to be 54.07 nm. The fluorescence studies in combination with GK-peptide and δ-Glu assay support the inhibition of AGEs by AG-Gnps. Based on the idea of gold nano-particle synthesis, it is anticipated, the toxicity of numerous drugs used at high doses can be diminished with additional efficiency.Communicated by Ramaswamy H. Sarma.The correlation between spiritual wellness and clinical outcomes is widely established in the literature. This thematic analysis illuminates the experiences of clinicians, chaplains, and parents of Neo-natal Intensive Care Unit (NICU) patients who participated in Compassion Rounds, spiritual care interventions that focus solely on emotional and spiritual well-being, rather than physical diagnoses. Clinicians and families participated in semi-structured interviews and focus groups. The results showed that Compassion Rounds had positive effects on spiritual wellness for NICU parents and their health care providers, while also allowing chaplains to model and provide spiritual care for physicians. Compassion Rounds enabled physicians to learn from chaplains and deliver effective spiritual wellness interventions within their limited available time. Compassion Rounds had a restorative effect on caregivers and have the potential to prevent or overcome burnout, return meaning to the work of clinicians, and create trust within multidisciplinary care teams.PURPOSE The purpose of this study was to capture information on patient experiences and perspectives of group medical appointments (GMAs) and compare them to those attending individual appointments (IAs) with the diabetes education team (usual care) for managing type 2 diabetes. METHODS Adults (N = 18; 61% male; 83% 50-70 years old ) with type 2 diabetes (or prediabetes) living in rural Saskatchewan were recruited to complete a semistructured interview on their experiences with GMAs or IAs. To be eligible to participate, individuals must have attended at least 2 GMAs or 2 IAs. Transcripts were coded and analyzed using content analysis. RESULTS Overall, participants spoke highly of their respective appointment type. Results indicated that both appointment types positively influenced understanding of diabetes management, with the most notable difference being greater understanding of stress management in the GMAs. Participants identified several positive aspects of each appointment type, which included convenience, supportive and enjoyable, and informative for GMAs and time and tailored information for IAs.
    ations on metastatic pattern, metastasis-free survival, and overall survival. © RSNA, 2020 See also the editorial by Choyke in this issue.Background The recently described "macrotrabecular-massive" (MTM) histologic subtype of hepatocellular carcinoma (HCC) (MTM-HCC) represents an aggressive form of HCC and is associated with poor survival. Purpose To investigate whether preoperative MRI can help identify MTM-HCCs in patients with HCC. Materials and Methods This retrospective study included patients with HCC treated with surgical resection between January 2008 and February 2018 and who underwent preoperative multiphase contrast material-enhanced MRI. Least absolute shrinkage and selection operator (LASSO)-penalized and multivariable logistic regression analyses were performed to identify clinical, biologic, and imaging features associated with the MTM-HCC subtype. Early recurrence (within 2 years) and overall recurrence were evaluated by using Kaplan-Meier analysis. Multivariable Cox regression analysis was performed to determine predictors of early and overall recurrence. Results One hundred fifty-two patients (median age, 64 years; interquartirecurrence. Conclusion At multiphase contrast-enhanced MRI, substantial necrosis helped identify macrotrabecular-massive hepatocellular carcinoma subtype with high specificity. © RSNA, 2020.Background Higher peak enhancement and washout component values measured on preoperative breast MRI scans with computer-aided diagnosis (CAD) are presumed to be associated with worse recurrence-free survival. Purpose To investigate whether CAD-extracted kinetic features of breast cancer and the heterogeneity of these features at preoperative MRI are associated with distant metastasis-free survival in women with invasive breast cancer. Materials and Methods Consecutive women with newly diagnosed invasive breast cancer who underwent preoperative MRI were retrospectively evaluated between 2011 and 2012. https://www.selleckchem.com/products/tasin-30.html A commercially available CAD system was used to extract the peak enhancement and delayed enhancement profiles of each breast cancer case from preoperative MRI data. The kinetic heterogeneity of these features (a measure of heterogeneity in the proportions of tumor pixels with delayed washout, plateau, and persistent components within a tumor) was calculated to evaluate intratumoral heterogeneity. Cox proportional Higher values of kinetic heterogeneity and peak enhancement as determined with computer-aided diagnosis of preoperative MRI were associated with worse distant metastasis-free survival in women with invasive breast cancer. © RSNA, 2020 See also the editorial by El Khouli and Jacobs in this issue.Aim To assess the potential of human induced pluripotent stem cell-derived smooth muscle cells (hiPSC-SMC) to accelerate diabetic wound healing. Methods hiPSC-SMC were embedded in 3D collagen scaffolds and cultured in vitro for 72 h; scaffolds were then applied to diabetic, nude mouse, splinted back wounds to assess in vivo healing. Cultured medium after scaffold incubation was collected and analyzed for expression of pro-angiogenic cytokines. Results hiPSC-SMC secrete increased concentration of pro-angiogenic cytokines, compared with murine adipose derived stem cells. Delivery of hiPSC-SMC-containing collagen scaffolds accelerates diabetic wound healing and is associated with an increased number of total and M2 type macrophages. Conclusion hiPSC-SMC promote angiogenesis and accelerate diabetic wound healing, making them a promising new candidate for treatment of diabetic wounds.The unavoidable glycation reaction is the major cause of diabetes and metabolic disorders. The glycation reaction is enhanced in case when the glycating agent is reactive carbonyl species (RCS) like, methylglyoxal (MG). The impact of RCS may result into the diabetes mellitus and its secondary complications along-with its role in cancers too. This reaction can be discontinued by using natural product inhibitors or by chemically synthesized drugs, like aminoguanidine (AG). However, AG is reported to be nephrotoxic (toxic to kidneys) at a concentration of 10 mM or more and has therefore serious health concerns. In the present study, bioconjugation of AG was done with the gold nanoparticles (Gnps) to mitigate its toxic effect and upsurge the efficacy of AG on RCS induced glycation. The AG-Gnps formed waas characterized by UV-Vis. spectroscopy and it reveals a peak at 529 nm corresponding to AG-gold nanoparticles. The particle size of the AG-Gnp was found to be 12 nm in TEM while in DLS it was found to be 54.07 nm. The fluorescence studies in combination with GK-peptide and δ-Glu assay support the inhibition of AGEs by AG-Gnps. Based on the idea of gold nano-particle synthesis, it is anticipated, the toxicity of numerous drugs used at high doses can be diminished with additional efficiency.Communicated by Ramaswamy H. Sarma.The correlation between spiritual wellness and clinical outcomes is widely established in the literature. This thematic analysis illuminates the experiences of clinicians, chaplains, and parents of Neo-natal Intensive Care Unit (NICU) patients who participated in Compassion Rounds, spiritual care interventions that focus solely on emotional and spiritual well-being, rather than physical diagnoses. Clinicians and families participated in semi-structured interviews and focus groups. The results showed that Compassion Rounds had positive effects on spiritual wellness for NICU parents and their health care providers, while also allowing chaplains to model and provide spiritual care for physicians. Compassion Rounds enabled physicians to learn from chaplains and deliver effective spiritual wellness interventions within their limited available time. Compassion Rounds had a restorative effect on caregivers and have the potential to prevent or overcome burnout, return meaning to the work of clinicians, and create trust within multidisciplinary care teams.PURPOSE The purpose of this study was to capture information on patient experiences and perspectives of group medical appointments (GMAs) and compare them to those attending individual appointments (IAs) with the diabetes education team (usual care) for managing type 2 diabetes. METHODS Adults (N = 18; 61% male; 83% 50-70 years old ) with type 2 diabetes (or prediabetes) living in rural Saskatchewan were recruited to complete a semistructured interview on their experiences with GMAs or IAs. To be eligible to participate, individuals must have attended at least 2 GMAs or 2 IAs. Transcripts were coded and analyzed using content analysis. RESULTS Overall, participants spoke highly of their respective appointment type. Results indicated that both appointment types positively influenced understanding of diabetes management, with the most notable difference being greater understanding of stress management in the GMAs. Participants identified several positive aspects of each appointment type, which included convenience, supportive and enjoyable, and informative for GMAs and time and tailored information for IAs.
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  • The activation of the Wnt/β-catenin pathway protected against the impairment of intestinal permeability induced by maternal vitamin D deficiency. CONCLUSIONS Maternal vitamin D deficiency increased intestinal permeability and decreased tight junction protein expression in offspring. The suppression of the Wnt/β-catenin signaling pathway through histone modification might be involved in the underlying mechanism. © 2020 American Society for Parenteral and Enteral Nutrition.Calcium metal batteries (CMBs) provide a promising option for high-energy and cost-effective energy storage technology beyond current state-of-the-art lithium-ion batteries. Nevertheless, the development of room-temperature CMBs is significantly impeded by the poor reversibility and short lifespan of calcium metal anode. Herein we report a solvation manipulation strategy to improve the plating/stripping reversibility of calcium metal anode by enhancing the de-solvation kinetics of calcium ions in the electrolyte. The introduction of lithium salt greatly changes the electrolyte structure by reducing coordination number of calcium ions in the first solvation shell. As a result, an unprecedented Coulombic efficiency (CE) of calcium metal anode for galvanostatic plating/stripping is achieved up to 99.1%, accompanying with a very stable long-term cycling performance over 200 cycles at room temperature. This work may open up a new opportunity for developing practical calcium metal batteries. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.OBJECTIVE Glucose-regulated protein 78 (GRP78) is an Endoplasmic Reticulum (ER) chaperone which has been shown that is overexpressed in cancer cells. Overexpression of GRP78 on cancer cells makes this molecule a suitable candidate for cancer detection and targeted therapy. VHH is the binding fragment of camelid heavy chain antibodies also known as "nanobody". The aim of this study is to isolate and produce a new recombinant nanobody using phage display technique to detect cancer cells. MATERIAL AND METHODS Using the c-terminal domain of GRP78 (CGRP) as an antigen, four rounds of biopanning were performed, and high-affinity binders were selected by ELISA. Their affinity and functionality were characterized by surface plasmon resonance (SPR) cell ELISA and immunocytochemistry. RESULTS A unique nanobody named V80 was purified. ELISA and SPR showed that this antibody had high specificity and affinity to the GRP78. Immunofluorescence analysis showed that V80 could specifically bind to the HepG2 and A549 cancer cell lines. CONCLUSION This novel recombinant nanobody could bind to the cell surface of different cancer cells. After further evaluation, this nanobody can be used as a new tool for cancer detection and tumor therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.This contribution reports light responsive catalytic nanoreactors based on poly(2-oxazoline) diblock copolymers. The hydrophobic block of the copolymer is a random copolymer consisting of a spiropyran functionalized 2-oxazoline (SPOx) and 2-(but-3-yn-1-yl)-4,5-dihydrooxazole (ButynOx), while the hydrophilic block is based on 2-methyl-2-oxazoline (MeOx). The block copolymer is terminated with tris(2-aminoethyl) amine (TREN) that serves as catalyst in a Knoevenagel condensation. Four block copolymers with different ButynOx/SPOx and hydrophilic/hydrophobic ratios are synthesized and self-assembled through solvent exchange. Micelles and vesicles of various sizes are observed by TEM, which undergo morphological and size changes in response to irradiation with UV light. https://www.selleckchem.com/products/pf-05221304.html We hypothesize that these transformations in the nanostructures are caused by increases in the hydrophilicity of the hydrophobic block when spiropyran (SP) isomerizes to merocyanine (**) in the presence of UV light. The reversible transition from micellar to vesicular nanoreactors resulted in increased reaction kinetics through improved substrate accessibility to the catalytic site, or termination of the catalytic reaction due to polymer precipitation. These nanoreactors present a promising platform towards photoregulating reaction outcomes based on changes in nanostructure morphology. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Radiation recall dermatitis (RRD) is an acute inflammatory skin reaction occurring in a skin area previously exposed to radiotherapy and triggered by subsequent intake of a drug, most commonly a chemotherapeutic agent. RRD secondary to antibiotics has also been reported but is a rare phenomenon overall and there are no reports of RRD in association with ceftriaxone exposure. METHODS We report on a 59-year-old patient who had received radiotherapy to the neck bilaterally and who developed RRD 6 months later after a single dose of intramuscular ceftriaxone. RESULTS The patient's rash resolved without further intervention over the ensuing 2 days following administration of a single dose of ceftriaxone. CONCLUSION This case illustrates that while RRD secondary to antibiotic exposure is rare, it is part of the differential diagnosis to be considered for acute dermatitis when there is a past history of radiotherapy to the same skin area. © 2020 Wiley Periodicals, Inc.BACKGROUND Treatment of drinking water may decrease microbial exposure. OBJECTIVE To investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases. METHODS We recruited 1,110 schoolchildren aged 6-16 years between 2011 and 2013 in Požega-Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells. We obtained data on microbial content of drinking water for all participants; 585 children were randomly selected for more detailed assessments, including skin ***** testing. Since water supply was highly correlated with rural residence, we compared clinical outcomes across four groups (Rural/Individual, Rural/Public, Urban/Individual and Urban/Public). For each child, we derived quantitative index of microbial exposure (bacterial load in the drinking water measured during the child's first year of life). RESULTS Cumulative bacterial load in drinking water was higher (median [IQR] 6390 [4190-9550] vs 0 [0-0]; P  less then  .
    The activation of the Wnt/β-catenin pathway protected against the impairment of intestinal permeability induced by maternal vitamin D deficiency. CONCLUSIONS Maternal vitamin D deficiency increased intestinal permeability and decreased tight junction protein expression in offspring. The suppression of the Wnt/β-catenin signaling pathway through histone modification might be involved in the underlying mechanism. © 2020 American Society for Parenteral and Enteral Nutrition.Calcium metal batteries (CMBs) provide a promising option for high-energy and cost-effective energy storage technology beyond current state-of-the-art lithium-ion batteries. Nevertheless, the development of room-temperature CMBs is significantly impeded by the poor reversibility and short lifespan of calcium metal anode. Herein we report a solvation manipulation strategy to improve the plating/stripping reversibility of calcium metal anode by enhancing the de-solvation kinetics of calcium ions in the electrolyte. The introduction of lithium salt greatly changes the electrolyte structure by reducing coordination number of calcium ions in the first solvation shell. As a result, an unprecedented Coulombic efficiency (CE) of calcium metal anode for galvanostatic plating/stripping is achieved up to 99.1%, accompanying with a very stable long-term cycling performance over 200 cycles at room temperature. This work may open up a new opportunity for developing practical calcium metal batteries. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.OBJECTIVE Glucose-regulated protein 78 (GRP78) is an Endoplasmic Reticulum (ER) chaperone which has been shown that is overexpressed in cancer cells. Overexpression of GRP78 on cancer cells makes this molecule a suitable candidate for cancer detection and targeted therapy. VHH is the binding fragment of camelid heavy chain antibodies also known as "nanobody". The aim of this study is to isolate and produce a new recombinant nanobody using phage display technique to detect cancer cells. MATERIAL AND METHODS Using the c-terminal domain of GRP78 (CGRP) as an antigen, four rounds of biopanning were performed, and high-affinity binders were selected by ELISA. Their affinity and functionality were characterized by surface plasmon resonance (SPR) cell ELISA and immunocytochemistry. RESULTS A unique nanobody named V80 was purified. ELISA and SPR showed that this antibody had high specificity and affinity to the GRP78. Immunofluorescence analysis showed that V80 could specifically bind to the HepG2 and A549 cancer cell lines. CONCLUSION This novel recombinant nanobody could bind to the cell surface of different cancer cells. After further evaluation, this nanobody can be used as a new tool for cancer detection and tumor therapy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.This contribution reports light responsive catalytic nanoreactors based on poly(2-oxazoline) diblock copolymers. The hydrophobic block of the copolymer is a random copolymer consisting of a spiropyran functionalized 2-oxazoline (SPOx) and 2-(but-3-yn-1-yl)-4,5-dihydrooxazole (ButynOx), while the hydrophilic block is based on 2-methyl-2-oxazoline (MeOx). The block copolymer is terminated with tris(2-aminoethyl) amine (TREN) that serves as catalyst in a Knoevenagel condensation. Four block copolymers with different ButynOx/SPOx and hydrophilic/hydrophobic ratios are synthesized and self-assembled through solvent exchange. Micelles and vesicles of various sizes are observed by TEM, which undergo morphological and size changes in response to irradiation with UV light. https://www.selleckchem.com/products/pf-05221304.html We hypothesize that these transformations in the nanostructures are caused by increases in the hydrophilicity of the hydrophobic block when spiropyran (SP) isomerizes to merocyanine (MC) in the presence of UV light. The reversible transition from micellar to vesicular nanoreactors resulted in increased reaction kinetics through improved substrate accessibility to the catalytic site, or termination of the catalytic reaction due to polymer precipitation. These nanoreactors present a promising platform towards photoregulating reaction outcomes based on changes in nanostructure morphology. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND Radiation recall dermatitis (RRD) is an acute inflammatory skin reaction occurring in a skin area previously exposed to radiotherapy and triggered by subsequent intake of a drug, most commonly a chemotherapeutic agent. RRD secondary to antibiotics has also been reported but is a rare phenomenon overall and there are no reports of RRD in association with ceftriaxone exposure. METHODS We report on a 59-year-old patient who had received radiotherapy to the neck bilaterally and who developed RRD 6 months later after a single dose of intramuscular ceftriaxone. RESULTS The patient's rash resolved without further intervention over the ensuing 2 days following administration of a single dose of ceftriaxone. CONCLUSION This case illustrates that while RRD secondary to antibiotic exposure is rare, it is part of the differential diagnosis to be considered for acute dermatitis when there is a past history of radiotherapy to the same skin area. © 2020 Wiley Periodicals, Inc.BACKGROUND Treatment of drinking water may decrease microbial exposure. OBJECTIVE To investigate whether bacterial load in drinking water is associated with altered risk of allergic diseases. METHODS We recruited 1,110 schoolchildren aged 6-16 years between 2011 and 2013 in Požega-Slavonia County in Croatia, where we capitalized on a natural experiment whereby individuals receive drinking water through public mains supply or individual wells. We obtained data on microbial content of drinking water for all participants; 585 children were randomly selected for more detailed assessments, including skin prick testing. Since water supply was highly correlated with rural residence, we compared clinical outcomes across four groups (Rural/Individual, Rural/Public, Urban/Individual and Urban/Public). For each child, we derived quantitative index of microbial exposure (bacterial load in the drinking water measured during the child's first year of life). RESULTS Cumulative bacterial load in drinking water was higher (median [IQR] 6390 [4190-9550] vs 0 [0-0]; P  less then  .
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  • Neuropeptide Y (NPY) controls energy homeostasis including orexigenic actions in mammalians and non-mammalians. Recently, NPY has attracted attention as a mediator of emotional behaviour and psychosomatic diseases. However, its functions are not fully understood. We established npy gene-deficient (NPY-KO) zebrafish (Danio rerio) to assess the relationship between NPY and emotional behaviours. The NPY-KO zebrafish exhibited similar growth, but pomc and avp mRNA levels in the brain were higher as compared to wild-type fish. NPY-KO zebrafish exhibited several anxiety-like behaviours, such as a decrease in social interaction in mirror test and decreased locomotion in black-white test. The acute cold stress-treated NPY-KO zebrafish exhibited anxiety-like behaviours such as remaining stationary and swimming along the side of the tank in the mirror test. Moreover, expression levels of anxiety-associated genes (orx and cck) and catecholamine production (gr, mr, th1 and th2) were significantly higher in NPY-KO zebrafish than in wild-type fish. We demonstrated that NPY-KO zebrafish have an anxiety phenotype and a stress-vulnerability like NPY-KO ****, whereby orx and/or catecholamine signalling may be involved in the mechanism actions.Digital rock physics combines microtomographic imaging with advanced numerical simulations of effective material properties. It is used to complement laboratory investigations with the aim to gain a deeper understanding of relevant physical processes related to transport and effective mechanical properties. We apply digital rock physics to reticulite, a natural mineral with a strong analogy to synthetic open-cell foams. We consider reticulite an end-member for high-porosity materials with a high stiffness and brittleness. For this specific material, hydro-mechanical experiments are very difficult to perform. Reticulite is a pyroclastic rock formed during intense Hawaiian fountaining events. The honeycombed network of bubbles is supported by glassy threads and forms a structure with a porosity of more than 80%. Comparing experimental with numerical results and theoretical estimates, we demonstrate the high potential of in situ characterization with respect to the investigation of effective material properties. We show that a digital rock physics workflow, so far applied to conventional rocks, yields reasonable results for high-porosity rocks and can be adopted for fabricated foam-like materials with similar properties. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html Numerically determined porosities, effective elastic properties, thermal conductivities and permeabilities of reticulite show a fair agreement to experimental results that required exeptionally high experimental efforts.Diabetes is a complex metabolic disorder and different environmental toxicants including heavy metals have been involved in diabetes induction. Therefore, assessment of the environmental risk factors and heavy metals induced toxicity have become critical for reducing the consequences of metals pollutants. Previously, we reported heavy metals induced nephrotoxicity in non-diabetic and diabetic rats. Here, we extended our analysis by examining the heavy metals induced organs (heart, kidney, liver, pancreas, and spleen) damage in diabetic and non-diabetic Wistar rats using histopathology and quantitative real-time PCR (qRT-PCR). Following the generation of the diabetic rat model, the animals were exposed to heavy metals including lead (Pb), arsenic (As), manganese (Mn) and cadmium (Cd). Both non-diabetic and diabetic rats were exposed to heavy metals for 30 days and subsequently, the heart, kidney, liver, pancreas and spleen tissues were examined. Heavy metal treatment resulted in irregularly arranged myofibrilsiabetic rats.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Plant nutritional  quality can influence interactions between herbivores and their parasitoids. While most previous work has focused on a limited set of secondary plant metabolites, the tri-trophic effects of overall phenotypic resistance have been understudied. Furthermore, the joint effects of secondary and primary metabolites on parasitoids are almost unexplored. In this study, we compared the performance and survival of the parasitoid species Asecodes parviclava Thompson on wild woodland strawberry (Fragaria vesca L.) genotypes showing variation in resistance against the parasitoid's host, the strawberry leaf beetle (Galerucella tenella L.). Additionally, we related the metabolic profiles of these plant genotypes to the tritrophic outcomes in order to identify primary and secondary metabolites involved in regulating plant potential to facilitate parasitism. We found that parasitoid performance was strongly affected by plant genotype, but those differences in plant resistance to the herbivore were not reflected in parasitoid survival. These findings could be explained in particular by a significant link between parasitoid survival and foliar carbohydrate levels, which appeared to be the most important compounds for parasitism success. The fact that plant quality strongly affects parasitism should be further explored and utilized in plant breeding programs for a synergistic application in sustainable pest management.Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization. Various cell mimics have been developed to establish fundamental engineering principles for the construction of artificial cells displaying cell-like organization, behaviour and complexity. However, collective phenomena, although of great importance for a better understanding of life-like behaviour, are underexplored. Here, we construct collectives of giant vesicles that can communicate with each other through diffusing chemical signals that are recognized and processed by synthetic enzymatic cascades. Similar to biological cells, the Receiver vesicles can transduce a weak signal originating from Sender vesicles into a strong response by virtue of a signal amplification step, which facilitates the propagation of signals over long distances within the artificial cell consortia. This design advances the development of interconnected artificial cells that can exchange metabolic and positional information to coordinate their higher-order organization.
    Neuropeptide Y (NPY) controls energy homeostasis including orexigenic actions in mammalians and non-mammalians. Recently, NPY has attracted attention as a mediator of emotional behaviour and psychosomatic diseases. However, its functions are not fully understood. We established npy gene-deficient (NPY-KO) zebrafish (Danio rerio) to assess the relationship between NPY and emotional behaviours. The NPY-KO zebrafish exhibited similar growth, but pomc and avp mRNA levels in the brain were higher as compared to wild-type fish. NPY-KO zebrafish exhibited several anxiety-like behaviours, such as a decrease in social interaction in mirror test and decreased locomotion in black-white test. The acute cold stress-treated NPY-KO zebrafish exhibited anxiety-like behaviours such as remaining stationary and swimming along the side of the tank in the mirror test. Moreover, expression levels of anxiety-associated genes (orx and cck) and catecholamine production (gr, mr, th1 and th2) were significantly higher in NPY-KO zebrafish than in wild-type fish. We demonstrated that NPY-KO zebrafish have an anxiety phenotype and a stress-vulnerability like NPY-KO mice, whereby orx and/or catecholamine signalling may be involved in the mechanism actions.Digital rock physics combines microtomographic imaging with advanced numerical simulations of effective material properties. It is used to complement laboratory investigations with the aim to gain a deeper understanding of relevant physical processes related to transport and effective mechanical properties. We apply digital rock physics to reticulite, a natural mineral with a strong analogy to synthetic open-cell foams. We consider reticulite an end-member for high-porosity materials with a high stiffness and brittleness. For this specific material, hydro-mechanical experiments are very difficult to perform. Reticulite is a pyroclastic rock formed during intense Hawaiian fountaining events. The honeycombed network of bubbles is supported by glassy threads and forms a structure with a porosity of more than 80%. Comparing experimental with numerical results and theoretical estimates, we demonstrate the high potential of in situ characterization with respect to the investigation of effective material properties. We show that a digital rock physics workflow, so far applied to conventional rocks, yields reasonable results for high-porosity rocks and can be adopted for fabricated foam-like materials with similar properties. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html Numerically determined porosities, effective elastic properties, thermal conductivities and permeabilities of reticulite show a fair agreement to experimental results that required exeptionally high experimental efforts.Diabetes is a complex metabolic disorder and different environmental toxicants including heavy metals have been involved in diabetes induction. Therefore, assessment of the environmental risk factors and heavy metals induced toxicity have become critical for reducing the consequences of metals pollutants. Previously, we reported heavy metals induced nephrotoxicity in non-diabetic and diabetic rats. Here, we extended our analysis by examining the heavy metals induced organs (heart, kidney, liver, pancreas, and spleen) damage in diabetic and non-diabetic Wistar rats using histopathology and quantitative real-time PCR (qRT-PCR). Following the generation of the diabetic rat model, the animals were exposed to heavy metals including lead (Pb), arsenic (As), manganese (Mn) and cadmium (Cd). Both non-diabetic and diabetic rats were exposed to heavy metals for 30 days and subsequently, the heart, kidney, liver, pancreas and spleen tissues were examined. Heavy metal treatment resulted in irregularly arranged myofibrilsiabetic rats.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Plant nutritional  quality can influence interactions between herbivores and their parasitoids. While most previous work has focused on a limited set of secondary plant metabolites, the tri-trophic effects of overall phenotypic resistance have been understudied. Furthermore, the joint effects of secondary and primary metabolites on parasitoids are almost unexplored. In this study, we compared the performance and survival of the parasitoid species Asecodes parviclava Thompson on wild woodland strawberry (Fragaria vesca L.) genotypes showing variation in resistance against the parasitoid's host, the strawberry leaf beetle (Galerucella tenella L.). Additionally, we related the metabolic profiles of these plant genotypes to the tritrophic outcomes in order to identify primary and secondary metabolites involved in regulating plant potential to facilitate parasitism. We found that parasitoid performance was strongly affected by plant genotype, but those differences in plant resistance to the herbivore were not reflected in parasitoid survival. These findings could be explained in particular by a significant link between parasitoid survival and foliar carbohydrate levels, which appeared to be the most important compounds for parasitism success. The fact that plant quality strongly affects parasitism should be further explored and utilized in plant breeding programs for a synergistic application in sustainable pest management.Multicellular organisms rely on intercellular communication to coordinate the behaviour of individual cells, which enables their differentiation and hierarchical organization. Various cell mimics have been developed to establish fundamental engineering principles for the construction of artificial cells displaying cell-like organization, behaviour and complexity. However, collective phenomena, although of great importance for a better understanding of life-like behaviour, are underexplored. Here, we construct collectives of giant vesicles that can communicate with each other through diffusing chemical signals that are recognized and processed by synthetic enzymatic cascades. Similar to biological cells, the Receiver vesicles can transduce a weak signal originating from Sender vesicles into a strong response by virtue of a signal amplification step, which facilitates the propagation of signals over long distances within the artificial cell consortia. This design advances the development of interconnected artificial cells that can exchange metabolic and positional information to coordinate their higher-order organization.
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  • nt. Epidermal growth factor receptor (EGFR) is a tyrosine kinase protein and plays a critical role in virus infection by modulating innate immunity. In this study, we cloned and sequenced the EGFR coding sequence of mandarin fish, designed as scEGFR, and explored its characteristics. scEGFR mRNA was widely expressed in the tested tissues of mandarin fish, and the higher mRNA levels were expressed in kidney and spleen. scEGFR expression was up-regulated in spleen and CPB cells at early stage of ISKNV and SCRV infection. Gefitinib (EGFR inhibitor) inhibited ISKNV and SCRV replication, and increased the expression of the interferon-stimulated genes (ISG). However the EGF (EGFR activator) promoted ISKNV and SCRV replication, and decreased the interferon-stimulated genes. Those results indicated that scEGFR and its signaling involved in ISKNV and SCRV infection, and EGFR activation negatively regulated the interferon response, providing a potential target for the development of new therapic strategy against ISKNV and SCRV. The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging 'return to normal' following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed. BACKGROUND/AIMS Whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of portal-pressure lowering effect in advanced cirrhosis is controversial. This study aimed to evaluate the systemic and splanchnic hemodynamic effects of β-blockers in decompensated vs compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. METHODS Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of cirrhosis decompensation (ascites with or without overt-encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting β-blockers and again after 1-to-3 months of treatment (short-term). RESULTS 403 patients were included, 190 decompensated and 213 compensated. At baseline, decompensated patients had higher portal-pressure than compensated patients and were more hyperdynamic, with e short-term effect of β-blockers on CO might adversely influence survival in decompensated cirrhosis, which suggests that careful dosage titration with non-invasive CO-monitoring might be helpful. BACKGROUND & AIMS Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver tests. METHODS Clinical records and laboratory results were obtained from 417 laboratory-confirmed COVID-19 patients who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. https://www.selleckchem.com/products/i-bet-762.html Information of clinical features of patients with abnormal liver tests were collected for analysis. RESULTS Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients raising liver enzyme levels to more than 3 times of upper limit units in alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase, respectively. Patients with abnormal liver test of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios (OR)=2.73, 95% confidence interval (CI) 1.19-6.3, and 4.44, 95% CI 1.93-10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both P less then 0.01). CONCLUSION Patients with abnormal liver tests had higher risks of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, should be monitored and evaluated frequently. Regulated cell death is intrinsically associated with inflammatory liver disease and is pivotal in governing outcomes of metabolic liver disease. Different types of cell death may coexist in the progression of metabolic liver disease to inflammation, fibrosis, and ultimately cirrhosis. In addition to apoptosis, lytic forms of hepatocellular death, such as necroptosis, pyroptosis and ferroptosis elicit strong inflammatory responses due to cell membrane permeabilization and release of cellular components, contributing to the recruitment of immune cells and activation of hepatic stellate cells. Controlling liver cell death, in turn, emerges with fundamental importance and offers novel opportunities for potential therapeutic intervention. This review summarizes the underlying mechanism of distinct lytic cell death modes and their commonalities, discusses its relevance to metabolic liver diseases of different aetiologies, and acknowledges the limitations of current knowledge in the field. We focus on the role of hepatocyte necroptosis, pyroptosis and ferroptosis in non-alcoholic fatty liver disease, alcohol-associated liver disease and other metabolic liver disorders, as well as potential of translation into human disease.
    nt. Epidermal growth factor receptor (EGFR) is a tyrosine kinase protein and plays a critical role in virus infection by modulating innate immunity. In this study, we cloned and sequenced the EGFR coding sequence of mandarin fish, designed as scEGFR, and explored its characteristics. scEGFR mRNA was widely expressed in the tested tissues of mandarin fish, and the higher mRNA levels were expressed in kidney and spleen. scEGFR expression was up-regulated in spleen and CPB cells at early stage of ISKNV and SCRV infection. Gefitinib (EGFR inhibitor) inhibited ISKNV and SCRV replication, and increased the expression of the interferon-stimulated genes (ISG). However the EGF (EGFR activator) promoted ISKNV and SCRV replication, and decreased the interferon-stimulated genes. Those results indicated that scEGFR and its signaling involved in ISKNV and SCRV infection, and EGFR activation negatively regulated the interferon response, providing a potential target for the development of new therapic strategy against ISKNV and SCRV. The coronavirus disease 2019 (COVID-19) pandemic has shattered the meticulously developed processes by which we delivered quality care for patients with cirrhosis. Care has been transformed by the crisis, but enduring lessons have been learned. In this article, we review how COVID-19 will impact cirrhosis care. We describe how this impact unfolds over 3 waves; i) an intense period with prioritized high-acuity care with delayed elective procedures and routine care during physical distancing, ii) a challenging 'return to normal' following the end of physical distancing, with increased emergent decompensations, morbidity, and systems of care overwhelmed by the backlog of deferred care, and iii) a protracted period of suboptimal outcomes characterized by missed diagnoses, progressive disease and loss to follow-up. We outline the concrete steps required to preserve the quality of care provided to patients with cirrhosis. This includes an intensification of the preventative care provided to patients with compensated cirrhosis, proactive chronic disease management, robust telehealth programs, and a reorganization of care delivery to provide a full service of care with flexible clinical staffing. Managing the pandemic of a serious chronic disease in the midst of a global infectious pandemic is challenging. It is incumbent upon the entire healthcare establishment to be strong enough to weather the storm. Change is needed. BACKGROUND/AIMS Whether the effect of β-blockers on arterial pressure and/or cardiac function may offset the benefit of portal-pressure lowering effect in advanced cirrhosis is controversial. This study aimed to evaluate the systemic and splanchnic hemodynamic effects of β-blockers in decompensated vs compensated cirrhosis and to investigate the influence of systemic hemodynamic changes on survival times in decompensated cirrhosis. METHODS Patients with cirrhosis and high-risk esophageal varices, without previous bleeding, were consecutively included and grouped according to the presence or absence of cirrhosis decompensation (ascites with or without overt-encephalopathy). Systemic and hepatic hemodynamic measurements were performed before starting β-blockers and again after 1-to-3 months of treatment (short-term). RESULTS 403 patients were included, 190 decompensated and 213 compensated. At baseline, decompensated patients had higher portal-pressure than compensated patients and were more hyperdynamic, with e short-term effect of β-blockers on CO might adversely influence survival in decompensated cirrhosis, which suggests that careful dosage titration with non-invasive CO-monitoring might be helpful. BACKGROUND & AIMS Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver tests. METHODS Clinical records and laboratory results were obtained from 417 laboratory-confirmed COVID-19 patients who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. https://www.selleckchem.com/products/i-bet-762.html Information of clinical features of patients with abnormal liver tests were collected for analysis. RESULTS Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients raising liver enzyme levels to more than 3 times of upper limit units in alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase, respectively. Patients with abnormal liver test of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios (OR)=2.73, 95% confidence interval (CI) 1.19-6.3, and 4.44, 95% CI 1.93-10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both P less then 0.01). CONCLUSION Patients with abnormal liver tests had higher risks of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, should be monitored and evaluated frequently. Regulated cell death is intrinsically associated with inflammatory liver disease and is pivotal in governing outcomes of metabolic liver disease. Different types of cell death may coexist in the progression of metabolic liver disease to inflammation, fibrosis, and ultimately cirrhosis. In addition to apoptosis, lytic forms of hepatocellular death, such as necroptosis, pyroptosis and ferroptosis elicit strong inflammatory responses due to cell membrane permeabilization and release of cellular components, contributing to the recruitment of immune cells and activation of hepatic stellate cells. Controlling liver cell death, in turn, emerges with fundamental importance and offers novel opportunities for potential therapeutic intervention. This review summarizes the underlying mechanism of distinct lytic cell death modes and their commonalities, discusses its relevance to metabolic liver diseases of different aetiologies, and acknowledges the limitations of current knowledge in the field. We focus on the role of hepatocyte necroptosis, pyroptosis and ferroptosis in non-alcoholic fatty liver disease, alcohol-associated liver disease and other metabolic liver disorders, as well as potential of translation into human disease.
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  • MicroRNA (miRNA) plays a pivotal role in cancer biology. Therefore, tumor suppressor (TS) miRNAs are an attractive target for cancer therapy. However, clinical trials have failed due to the difficulties in miRNA delivery, warranting the development of a novel drug delivery system (DDS). https://www.selleckchem.com/products/bt-11.html Exosomes are stable in circulation and selectively picked up by cancer cells, indicating that they can serve as a miRNA carrier. The aim of this study was to explore the possibility of exosomes as a carrier for miRNA replacement therapy for ovarian cancer (OC). First, exosomes were purified from primary-cultured omental fibroblasts of OC patients. miR-199a-3p was selected as a TS miRNA, and the synthesized miR-199a-3p was loaded into exosomes by electroporation. Treatment with miR199a-3p-loaded-exosomes (miR-199a-3p-Exo) drastically increased miR-199a-3p expression level in OC cell lines (CaOV3; 8592-, SKOV3; 67188-, and OVCAR3; 2280-fold). miR-199a-3p-Exo suppressed c-Met expression, a direct target of miR-199a-3p, and thereby inhibited cell proliferation and invasion. In a xenograft study, miR-199a-3p-Exo also drastically inhibited peritoneal dissemination in OC **** model, and diminished c-Met expression, ERK phosphorylation, and MMP2 expression in tumors. These results suggest that miRNA replacement therapy using exosomes shows promise for treatment of OC. Given that omental fibroblasts can be obtained from most OC patients, patient-derived exosomes can be utilized as a DDS for future molecular-targeted therapies.Myocardial infarction (MI) remains a major health-related problem with high incidence and mortality rates. Oxidative stress plays an important role in myocardial ischemia injury and further leads to myocardial remodeling. Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factors that regulate a variety of biological functions. However the function of bFGF in myocardial infarction is still unknown. Here we aimed to investigate the role of bFGF and its underlying mechanism in ischemia heart and cardiomyocytes apoptosis. We found that bFGF treatment could significantly enhance the cardioprotective effects by reducing oxidative stress both in vivo and vitro. In addition, we found that bFGF activated Nrf2-mediated antioxidant defenses via Akt/GSK3β/Fyn pathway. Furthermore, Nrf2 knockdown largely counteracted the protective effect of bFGF. In summary, our study suggested that bFGF could alleviate myocardial infarction injury and cardiomyocytes apoptosis via Nrf2.The mitochondrial translation process, in which mitochondrial DNA (mtDNA)-encoded genes are translated into their corresponding proteins, is crucial for mitochondrial function, biogenesis, and integrity. This process is divided into four phases-initiation, elongation, termination, and mitoribosome recycling-which are regulated by specific translation factors, including mitochondrial initiation factor 2 and 3 (mtIF2 and mtIF3), mitochondrial elongation factor Tu, Ts, and G1 (mtEFTu, mtEFTs, and mtEFG1), mitochondrial translational release factor 1-like (mtRF1L), and mitochondrial recycling factor 1 and 2 (mtRRF1 and mtRRF2). Muscle denervation downregulates mitochondrial biomass and induces skeletal muscle atrophy. However, it is unknown whether denervation affects the expression of mitochondrial translation factors in skeletal muscle. In this study, we hypothesized that denervation decreases the expression of mitochondrial translation factors. Therefore, we investigated the effect of muscle denervation on mitochondrial protein and mitochondrial translation factor expression in soleus muscle after surgery. Denervation induced muscle atrophy and activated the ubiquitin-proteasome pathway in soleus muscle. Additionally, muscle denervation decreased the expression of mitochondrial translation factors as well as nuclear DNA and mtDNA-encoded mitochondrial proteins in soleus muscle. Further, a correlation was found between the expression of mitochondrial translation factors and mtDNA-encoded proteins three and seven days after denervation. Taken together, these results demonstrated that the denervation-induced decrease in mitochondrial biogenesis corresponded with changes in mitochondrial translation factors in murine skeletal muscle, providing novel molecular-level insight into the effects of muscle denervation on the mitochondrial translation process.Diabetes has been associated with metabolic disorder, insulin resistance and neuroinflammation. However, the pathogenesis for HFD-induced injury of central nervous system (CNS) is still unclear. Tripartite Motif Containing 13 (TRIM13), also known as RFP2, is a member of TRIM proteins, and is associated with multiple cellular processes, such as apoptosis, survival and inflammation. However, the effects of TRIM13 on brain injury, especially the HFD-induced CNS damage, have not been investigated. To address this issue, the TRIM13flox/flox (fl/fl) **** were produced and then crossed them with Nestin-Cre **** to delete TRIM13 specifically in the brain (cKO). Then, T2D **** with obesity were established by chronic feeding of HFD. We found that brain-specific deletion of TRIM13 accelerated HFD-induced metabolic disorder, insulin resistance and systematic inflammatory response. In addition, HFDcKO **** exhibited significantly higher pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis faemonstrated that TRIM13 was involved in HFD-induced CNS injury and insulin resistance through regulating neuroinflammatory response, contributing to the modulation of peripheral metabolic disorders.Objective To investigate the expression of Nogo-A in dorsal root ganglion (DRG) in rats with cauda equina injury and the therapeutic effects of blocking Nogo-A and its receptor. Methods and materials Fifty-eight male Sprague-Dawley rats were divided randomly into either the sham operation group (n = 24) or the cauda equina compression (CEC) control group (n = 34). Behavioral, histological, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses were conducted to assess the establishment of the model. The dynamic expression change of Nogo-A was evaluated using real time-qPCR. Immunofluorescence was used to evaluate the expression of Nogo-A in the DRG and cauda equina. Furthermore, 20 male Sprague-Dawley rats were equally divided into 4 groups, including the sham group, the CEC group, the NEP1-40 (the NgR antagonist peptide) treatment group, and the JTE-013 (the S1PR2 antagonist) treatment group. Behavioral assessments and western blotting were used to evaluate the therapeutic effect of cauda equina injury via blocking Nogo-A and its receptor.
    MicroRNA (miRNA) plays a pivotal role in cancer biology. Therefore, tumor suppressor (TS) miRNAs are an attractive target for cancer therapy. However, clinical trials have failed due to the difficulties in miRNA delivery, warranting the development of a novel drug delivery system (DDS). https://www.selleckchem.com/products/bt-11.html Exosomes are stable in circulation and selectively picked up by cancer cells, indicating that they can serve as a miRNA carrier. The aim of this study was to explore the possibility of exosomes as a carrier for miRNA replacement therapy for ovarian cancer (OC). First, exosomes were purified from primary-cultured omental fibroblasts of OC patients. miR-199a-3p was selected as a TS miRNA, and the synthesized miR-199a-3p was loaded into exosomes by electroporation. Treatment with miR199a-3p-loaded-exosomes (miR-199a-3p-Exo) drastically increased miR-199a-3p expression level in OC cell lines (CaOV3; 8592-, SKOV3; 67188-, and OVCAR3; 2280-fold). miR-199a-3p-Exo suppressed c-Met expression, a direct target of miR-199a-3p, and thereby inhibited cell proliferation and invasion. In a xenograft study, miR-199a-3p-Exo also drastically inhibited peritoneal dissemination in OC mice model, and diminished c-Met expression, ERK phosphorylation, and MMP2 expression in tumors. These results suggest that miRNA replacement therapy using exosomes shows promise for treatment of OC. Given that omental fibroblasts can be obtained from most OC patients, patient-derived exosomes can be utilized as a DDS for future molecular-targeted therapies.Myocardial infarction (MI) remains a major health-related problem with high incidence and mortality rates. Oxidative stress plays an important role in myocardial ischemia injury and further leads to myocardial remodeling. Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factors that regulate a variety of biological functions. However the function of bFGF in myocardial infarction is still unknown. Here we aimed to investigate the role of bFGF and its underlying mechanism in ischemia heart and cardiomyocytes apoptosis. We found that bFGF treatment could significantly enhance the cardioprotective effects by reducing oxidative stress both in vivo and vitro. In addition, we found that bFGF activated Nrf2-mediated antioxidant defenses via Akt/GSK3β/Fyn pathway. Furthermore, Nrf2 knockdown largely counteracted the protective effect of bFGF. In summary, our study suggested that bFGF could alleviate myocardial infarction injury and cardiomyocytes apoptosis via Nrf2.The mitochondrial translation process, in which mitochondrial DNA (mtDNA)-encoded genes are translated into their corresponding proteins, is crucial for mitochondrial function, biogenesis, and integrity. This process is divided into four phases-initiation, elongation, termination, and mitoribosome recycling-which are regulated by specific translation factors, including mitochondrial initiation factor 2 and 3 (mtIF2 and mtIF3), mitochondrial elongation factor Tu, Ts, and G1 (mtEFTu, mtEFTs, and mtEFG1), mitochondrial translational release factor 1-like (mtRF1L), and mitochondrial recycling factor 1 and 2 (mtRRF1 and mtRRF2). Muscle denervation downregulates mitochondrial biomass and induces skeletal muscle atrophy. However, it is unknown whether denervation affects the expression of mitochondrial translation factors in skeletal muscle. In this study, we hypothesized that denervation decreases the expression of mitochondrial translation factors. Therefore, we investigated the effect of muscle denervation on mitochondrial protein and mitochondrial translation factor expression in soleus muscle after surgery. Denervation induced muscle atrophy and activated the ubiquitin-proteasome pathway in soleus muscle. Additionally, muscle denervation decreased the expression of mitochondrial translation factors as well as nuclear DNA and mtDNA-encoded mitochondrial proteins in soleus muscle. Further, a correlation was found between the expression of mitochondrial translation factors and mtDNA-encoded proteins three and seven days after denervation. Taken together, these results demonstrated that the denervation-induced decrease in mitochondrial biogenesis corresponded with changes in mitochondrial translation factors in murine skeletal muscle, providing novel molecular-level insight into the effects of muscle denervation on the mitochondrial translation process.Diabetes has been associated with metabolic disorder, insulin resistance and neuroinflammation. However, the pathogenesis for HFD-induced injury of central nervous system (CNS) is still unclear. Tripartite Motif Containing 13 (TRIM13), also known as RFP2, is a member of TRIM proteins, and is associated with multiple cellular processes, such as apoptosis, survival and inflammation. However, the effects of TRIM13 on brain injury, especially the HFD-induced CNS damage, have not been investigated. To address this issue, the TRIM13flox/flox (fl/fl) mice were produced and then crossed them with Nestin-Cre mice to delete TRIM13 specifically in the brain (cKO). Then, T2D mice with obesity were established by chronic feeding of HFD. We found that brain-specific deletion of TRIM13 accelerated HFD-induced metabolic disorder, insulin resistance and systematic inflammatory response. In addition, HFDcKO mice exhibited significantly higher pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β and tumor necrosis faemonstrated that TRIM13 was involved in HFD-induced CNS injury and insulin resistance through regulating neuroinflammatory response, contributing to the modulation of peripheral metabolic disorders.Objective To investigate the expression of Nogo-A in dorsal root ganglion (DRG) in rats with cauda equina injury and the therapeutic effects of blocking Nogo-A and its receptor. Methods and materials Fifty-eight male Sprague-Dawley rats were divided randomly into either the sham operation group (n = 24) or the cauda equina compression (CEC) control group (n = 34). Behavioral, histological, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses were conducted to assess the establishment of the model. The dynamic expression change of Nogo-A was evaluated using real time-qPCR. Immunofluorescence was used to evaluate the expression of Nogo-A in the DRG and cauda equina. Furthermore, 20 male Sprague-Dawley rats were equally divided into 4 groups, including the sham group, the CEC group, the NEP1-40 (the NgR antagonist peptide) treatment group, and the JTE-013 (the S1PR2 antagonist) treatment group. Behavioral assessments and western blotting were used to evaluate the therapeutic effect of cauda equina injury via blocking Nogo-A and its receptor.
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  • OBJECTIVES This study assessed the feasibility and outcomes of performing robotic cardiac surgery without lung isolation using single-lumen (SL) endotracheal tube intubation. METHODS Between 2013 and 2017, 132 patients underwent robotically-assisted atrial septal defect closure. A retrospective analysis was performed of 23 patients (11 males, mean age 30.9 ± 5 years) who underwent robotic surgery with double-lumen (DL) endotracheal tube intubation (group 1) compared with 109 patients (57 males, mean age 32.4 ± 7.5 years) undergoing the same procedure with SL endotracheal intubation (group 2). The patient groups were compared in terms of demographic characteristics, operative data, and complications. The technical feasibility of the robotic procedure without lung isolation was evaluated. RESULTS There were no mortality, intraoperative complication, and conversion. Mean total anesthesia time was significantly decreased in the SL intubation group (238.3 ± 22.4 vs 227.2 ± 21.2 minutes; P = .025). First-pass intubation success was significantly higher in the SL intubation group (17 [73.9%] vs 98 [89.9%] patients; P = .032). Mean ventilation time (10.9 ± 5.3 hours), intensive care unit stay (16.8 ± 10.1 hours), and the length of hospital stay (3.8 ± 1.2 days) was significantly decreased in patients with SL tube (P  less then  .05). Unilateral reexpansion pulmonary edema was observed in five (21.7%) patients with DL tube, whereas no patient with SL tube had this complication. CONCLUSIONS SL endotracheal tube intubation without lung isolation is a feasible and safe airway alternative in robotic cardiac procedures. This approach resulted in shorter anesthesia time, ventilation time and the length of hospital stay. Port placement and robotic set-up can be uneventfully performed without lung isolation. © 2020 Wiley Periodicals, Inc.Impairments in both executive function and parent-child interactions are associated with child externalizing behavior, but few studies have tested the uniqueness of these associations in the first years of life. Addressing these gaps, the current study involved an international sample (N = 438; 218 boys) who, at 14 and 24 months, completed an innovative battery of executive function tasks and were filmed at home in dyadic interaction with their mothers, enabling detailed observational ratings of maternal support. In addition, parents rated infant temperament at 4 months and externalizing behavior at 14 and 24 months. Cross-lagged longitudinal analysis showed a unidirectional developmental association between executive function at 14 months and externalizing behavior at 24 months. In addition, infant negative affect moderated the inverse association between maternal support at 14 months and externalizing behavior at 24 months. The benefits of maternal support were only evident for children with low levels of negative affect in infancy. We discuss this finding in relation to theoretical models that highlight child effects (e.g., models of vantage sensitivity). This article is protected by copyright. All rights reserved.Understanding the origins of morphological specializations in mammals is a key goal in evolutionary biology. It can be accomplished by studying dental homology, which is at the core of most evolutionary and developmental studies. Here, we focused on the evolution and development of the specialized dentition of hyraxes for which dental homologies have long been debated, and could have implications on early placental evolution. Specifically, we analysed dental mineralization sequences of the three living genera of hyraxes and 17 fossil species using X-ray computed microtomography. Our results point out the labile position of vestigial upper teeth on jaw bones in extant species, associated with the frequently unusual premolar shape of deciduous canines over 50 Ma of hyracoid evolution. We proposed two evolutionary and developmental hypotheses to explain these original hyracoid dental characteristics. (a) The presence of a vestigial teeth on the maxilla in front of a complex deciduous canine could be interpreted as extra-teeth reminiscent of early placental evolution or sirenians, an order phylogenetically close to hyracoids and showing five premolars. (b) These vestigial teeth could also correspond to third incisors with a position unusually shifted on the maxilla, which could be explained by the dual developmental origin of these most posterior incisors and their degenerated condition. This integrative study allows discussion on the current evolutionary and developmental paradigms associated with the mammalian dentition. It also highlights the importance of nonmodel species to understand dental homologies. © 2020 Wiley Periodicals, Inc.BACKGROUND Pilonidal sinus disease (PSD) is commonly seen in young adults but may also affect adolescents. Our goal was to present results from operated patients, with a focus on the original Limberg flap that we have standardised for the first time. METHODS This study was a retrospective review of 60 teenaged patients who underwent surgery in a single paediatric surgery centre over approximately 15 years. RESULTS Of the 60 patients, 33 (55%) were male and the mean age was 14.20 ± 1.31 (9-17) years. After pilonidal sinus excision, primary repair and Limberg flap were performed in patients, 45 (75%) and 15 (25%) respectively. There were no complications in the patients who underwent the Limberg flap technique, while 49% of the patients who underwent primary repair exhibited complications. The mean follow-up was 6.7 ± 4.8 years. CONCLUSION We standardised the Limberg flap for the first time in children with measurements and considered that it meets ideal expectations not difficult to perform, low complication and recurrence rates, acceptable time to return to normal activities and satisfactory cosmetic results. https://www.selleckchem.com/products/cynarin.html We did not identify fewer complications in patients treated with the standard original Limberg flap with epilation, a finding that is comparable with all of the treatment methods reported in the literature related with children. This article is protected by copyright. All rights reserved.
    OBJECTIVES This study assessed the feasibility and outcomes of performing robotic cardiac surgery without lung isolation using single-lumen (SL) endotracheal tube intubation. METHODS Between 2013 and 2017, 132 patients underwent robotically-assisted atrial septal defect closure. A retrospective analysis was performed of 23 patients (11 males, mean age 30.9 ± 5 years) who underwent robotic surgery with double-lumen (DL) endotracheal tube intubation (group 1) compared with 109 patients (57 males, mean age 32.4 ± 7.5 years) undergoing the same procedure with SL endotracheal intubation (group 2). The patient groups were compared in terms of demographic characteristics, operative data, and complications. The technical feasibility of the robotic procedure without lung isolation was evaluated. RESULTS There were no mortality, intraoperative complication, and conversion. Mean total anesthesia time was significantly decreased in the SL intubation group (238.3 ± 22.4 vs 227.2 ± 21.2 minutes; P = .025). First-pass intubation success was significantly higher in the SL intubation group (17 [73.9%] vs 98 [89.9%] patients; P = .032). Mean ventilation time (10.9 ± 5.3 hours), intensive care unit stay (16.8 ± 10.1 hours), and the length of hospital stay (3.8 ± 1.2 days) was significantly decreased in patients with SL tube (P  less then  .05). Unilateral reexpansion pulmonary edema was observed in five (21.7%) patients with DL tube, whereas no patient with SL tube had this complication. CONCLUSIONS SL endotracheal tube intubation without lung isolation is a feasible and safe airway alternative in robotic cardiac procedures. This approach resulted in shorter anesthesia time, ventilation time and the length of hospital stay. Port placement and robotic set-up can be uneventfully performed without lung isolation. © 2020 Wiley Periodicals, Inc.Impairments in both executive function and parent-child interactions are associated with child externalizing behavior, but few studies have tested the uniqueness of these associations in the first years of life. Addressing these gaps, the current study involved an international sample (N = 438; 218 boys) who, at 14 and 24 months, completed an innovative battery of executive function tasks and were filmed at home in dyadic interaction with their mothers, enabling detailed observational ratings of maternal support. In addition, parents rated infant temperament at 4 months and externalizing behavior at 14 and 24 months. Cross-lagged longitudinal analysis showed a unidirectional developmental association between executive function at 14 months and externalizing behavior at 24 months. In addition, infant negative affect moderated the inverse association between maternal support at 14 months and externalizing behavior at 24 months. The benefits of maternal support were only evident for children with low levels of negative affect in infancy. We discuss this finding in relation to theoretical models that highlight child effects (e.g., models of vantage sensitivity). This article is protected by copyright. All rights reserved.Understanding the origins of morphological specializations in mammals is a key goal in evolutionary biology. It can be accomplished by studying dental homology, which is at the core of most evolutionary and developmental studies. Here, we focused on the evolution and development of the specialized dentition of hyraxes for which dental homologies have long been debated, and could have implications on early placental evolution. Specifically, we analysed dental mineralization sequences of the three living genera of hyraxes and 17 fossil species using X-ray computed microtomography. Our results point out the labile position of vestigial upper teeth on jaw bones in extant species, associated with the frequently unusual premolar shape of deciduous canines over 50 Ma of hyracoid evolution. We proposed two evolutionary and developmental hypotheses to explain these original hyracoid dental characteristics. (a) The presence of a vestigial teeth on the maxilla in front of a complex deciduous canine could be interpreted as extra-teeth reminiscent of early placental evolution or sirenians, an order phylogenetically close to hyracoids and showing five premolars. (b) These vestigial teeth could also correspond to third incisors with a position unusually shifted on the maxilla, which could be explained by the dual developmental origin of these most posterior incisors and their degenerated condition. This integrative study allows discussion on the current evolutionary and developmental paradigms associated with the mammalian dentition. It also highlights the importance of nonmodel species to understand dental homologies. © 2020 Wiley Periodicals, Inc.BACKGROUND Pilonidal sinus disease (PSD) is commonly seen in young adults but may also affect adolescents. Our goal was to present results from operated patients, with a focus on the original Limberg flap that we have standardised for the first time. METHODS This study was a retrospective review of 60 teenaged patients who underwent surgery in a single paediatric surgery centre over approximately 15 years. RESULTS Of the 60 patients, 33 (55%) were male and the mean age was 14.20 ± 1.31 (9-17) years. After pilonidal sinus excision, primary repair and Limberg flap were performed in patients, 45 (75%) and 15 (25%) respectively. There were no complications in the patients who underwent the Limberg flap technique, while 49% of the patients who underwent primary repair exhibited complications. The mean follow-up was 6.7 ± 4.8 years. CONCLUSION We standardised the Limberg flap for the first time in children with measurements and considered that it meets ideal expectations not difficult to perform, low complication and recurrence rates, acceptable time to return to normal activities and satisfactory cosmetic results. https://www.selleckchem.com/products/cynarin.html We did not identify fewer complications in patients treated with the standard original Limberg flap with epilation, a finding that is comparable with all of the treatment methods reported in the literature related with children. This article is protected by copyright. All rights reserved.
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  • The human positive coactivator 4 (PC4) was originally identified as a multi-functional cofactor capable of mediating transcription activation by diverse gene- and tissue-specific activators. Recent studies suggest that PC4 might also function as a novel cancer biomarker and therapeutic target for different types of cancers. siRNA knockdown studies indicated that down-regulation of PC4 expression could inhibit tumorigeneicity of A549 non-small cell lung cancer tumor model in nude ****. Here we show that AG-1031, a small molecule identified by high throughput screening, can inhibit the double-stranded DNA binding activity of PC4, more effectively than its single-stranded DNA binding activity. AG-1031 also specifically inhibited PC4-dependent transcriptional activation in vitro using purified transcription factors. AG-1031 inhibited proliferation of several cultured cell lines derived from non-small cell lung cancers (NSCLC) and growth of tumors that formed from A549 cell xenografts in immuno-compromised ****. Moreover, pre-injection of AG-1031 in these **** not only reduced tumor size, but also prevented tumor formation in 20% of the animals. AG-1031 treated A549 cells and tumors from AG-1031 treated animals showed a significant decrease in the levels of both PC4 and VEGFC, a key mediator of angiogenesis in cancer. On the other hand, all tested **** remained constant weight during animal trials. These results demonstrated that AG-1031 could be a potential therapy for PC4-positive NSCLC.The specification of cell identity depends on the exposure of cells to sequences of bioactive ligands. All-trans retinoic acid (ATRA) affects neuronal development in the early stage, and it is involved in neuronal lineage reprogramming. We previously established a fibroblast-like dedifferentiated fat cells (DFATs) derived from highly homogeneous mature adipocytes, which are more suitable for the study of cellular reprogramming. Canine cognitive dysfunction is similar to human cognitive dysfunction, suggesting that dogs could be a pathological and pharmacological model for human neuronal diseases. However, the effect of ATRA on neuronal reprogramming in dogs has remained unclear. Therefore, in this study, we investigated the effect of ATRA on the neuronal reprogramming of canine DFATs. ATRA induced the expression of neuronal marker mRNA/protein. The neuron-like cells showed Ca2+ influx with depolarization (50 mM KCl; 84.75 ± 4.05%) and Na+ channel activation (50 μM veratridine; 96.02 ± 2.02%). Optical imaging of presynaptic terminal activity and detection of neurotransmitter release showed that the neuron-like cells exhibited the GABAergic neuronal property. Genome-wide RNA-sequencing analysis shows that the transcriptome profile of canine DFATs is effectively reprogrammed towards that of cortical interneuron lineage. Collectively, ATRA can produce functional GABAergic cortical interneuron-like cells from canine DFATs, exhibiting neuronal function with > 80% efficiency. We further demonstrated the contribution of JNK3 to ATRA-induced neuronal reprogramming in canine DFATs. In conclusion, the neuron-like cells from canine DFATs could be a powerful tool for translational research in cell transplantation therapy, in vitro disease modeling, and drug screening for neuronal diseases.Salmonella Heidelberg is commonly reported in foodborne outbreaks around the world, and chickens and poultry products are known as important source of these pathogen. Multidrug-resistant S. Heidelberg strains are disseminated into poultry production chair, which can lead to severe clinical infections in humans and of difficult to treat. This study aimed at evaluating the β-lactam susceptibility and genotypic relatedness of Salmonella Heidelberg at Brazilian poultry production chain. Sixty-two S. Heidelberg strains from poultry production chain (poultry, poultry meat and poultry farm) were used. All strains were evaluated to antimicrobial susceptibility by diffusion disk test, as well as β-lactam resistance genes. Genotypic relatedness was assessed by Pulsed-Field Gel Eletrophoresis, using Xba1 restriction enzyme. Forty-one strains were characterized as multidrug-resistant according to phenotype characterization. The resistance susceptibility revealed 31 distinct profiles, with higher prevalence of streptomycin (61/62), nalidixic acid (50/62), tetracycline (43/62) and β-lactam drugs (37/62). blaCMY-2 was the more frequent β-lactamase gene found (38/62); other resistance genes found were blaCTX-M (2/62), blaSHV (3/62) and blaTEM-1 (38/62). No carbapenemase genes was found. The Pulsed-Field Gel Electrophoresis showed 58 different profiles. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html Strains with a larger number of antimicrobial resistance were grouped into ten major clusters apart from others. The spread of resistance by ampC continues to rise, thereby turning concern to public health, since the β-lactam antimicrobials are used as a therapeutic treatment in humans.Oral pre-exposure prophylaxis (PrEP) for HIV-negative individuals at high risk was introduced in Lesotho in April 2016. To assess the feasibility and acceptability of PrEP in Lesotho and to study the attitudes and beliefs around HIV risk and prevention measures among young women, between September and December 2016 we asked 302 female university students at fourteen higher education institutions in Lesotho about their sexual behavior, experiences of sexual coercion and abuse, HIV risk perception, willingness to use PrEP, as well as their attitudes toward condom use and self-administration of daily medications. Overall, 57.3% of the sample reported perceiving themselves at risk of acquiring HIV and 32.1% reported being strongly willing to use PrEP if it were available in their community. In a multivariate mediation analysis, perceived HIV risk was associated with 11.5 percentage points increase in likelihood of using PrEP (p = 0.041). Multiple concurrent sexual partnership was associated with 16.1 percentage pd not report IPV in their network of peers (p = 0.009). These findings support the inclusion of individuals with multiple concurrent sexual partners among the key populations for PrEP provision and confirm that willingness to use PrEP is not solely driven by HIV risk perception. They also indicate that the presence of IPV in peer networks is related to one's willingness to use PrEP. PrEP service provision may generate synergies with IPV prevention programs when offered within this framework.
    The human positive coactivator 4 (PC4) was originally identified as a multi-functional cofactor capable of mediating transcription activation by diverse gene- and tissue-specific activators. Recent studies suggest that PC4 might also function as a novel cancer biomarker and therapeutic target for different types of cancers. siRNA knockdown studies indicated that down-regulation of PC4 expression could inhibit tumorigeneicity of A549 non-small cell lung cancer tumor model in nude mice. Here we show that AG-1031, a small molecule identified by high throughput screening, can inhibit the double-stranded DNA binding activity of PC4, more effectively than its single-stranded DNA binding activity. AG-1031 also specifically inhibited PC4-dependent transcriptional activation in vitro using purified transcription factors. AG-1031 inhibited proliferation of several cultured cell lines derived from non-small cell lung cancers (NSCLC) and growth of tumors that formed from A549 cell xenografts in immuno-compromised mice. Moreover, pre-injection of AG-1031 in these mice not only reduced tumor size, but also prevented tumor formation in 20% of the animals. AG-1031 treated A549 cells and tumors from AG-1031 treated animals showed a significant decrease in the levels of both PC4 and VEGFC, a key mediator of angiogenesis in cancer. On the other hand, all tested mice remained constant weight during animal trials. These results demonstrated that AG-1031 could be a potential therapy for PC4-positive NSCLC.The specification of cell identity depends on the exposure of cells to sequences of bioactive ligands. All-trans retinoic acid (ATRA) affects neuronal development in the early stage, and it is involved in neuronal lineage reprogramming. We previously established a fibroblast-like dedifferentiated fat cells (DFATs) derived from highly homogeneous mature adipocytes, which are more suitable for the study of cellular reprogramming. Canine cognitive dysfunction is similar to human cognitive dysfunction, suggesting that dogs could be a pathological and pharmacological model for human neuronal diseases. However, the effect of ATRA on neuronal reprogramming in dogs has remained unclear. Therefore, in this study, we investigated the effect of ATRA on the neuronal reprogramming of canine DFATs. ATRA induced the expression of neuronal marker mRNA/protein. The neuron-like cells showed Ca2+ influx with depolarization (50 mM KCl; 84.75 ± 4.05%) and Na+ channel activation (50 μM veratridine; 96.02 ± 2.02%). Optical imaging of presynaptic terminal activity and detection of neurotransmitter release showed that the neuron-like cells exhibited the GABAergic neuronal property. Genome-wide RNA-sequencing analysis shows that the transcriptome profile of canine DFATs is effectively reprogrammed towards that of cortical interneuron lineage. Collectively, ATRA can produce functional GABAergic cortical interneuron-like cells from canine DFATs, exhibiting neuronal function with > 80% efficiency. We further demonstrated the contribution of JNK3 to ATRA-induced neuronal reprogramming in canine DFATs. In conclusion, the neuron-like cells from canine DFATs could be a powerful tool for translational research in cell transplantation therapy, in vitro disease modeling, and drug screening for neuronal diseases.Salmonella Heidelberg is commonly reported in foodborne outbreaks around the world, and chickens and poultry products are known as important source of these pathogen. Multidrug-resistant S. Heidelberg strains are disseminated into poultry production chair, which can lead to severe clinical infections in humans and of difficult to treat. This study aimed at evaluating the β-lactam susceptibility and genotypic relatedness of Salmonella Heidelberg at Brazilian poultry production chain. Sixty-two S. Heidelberg strains from poultry production chain (poultry, poultry meat and poultry farm) were used. All strains were evaluated to antimicrobial susceptibility by diffusion disk test, as well as β-lactam resistance genes. Genotypic relatedness was assessed by Pulsed-Field Gel Eletrophoresis, using Xba1 restriction enzyme. Forty-one strains were characterized as multidrug-resistant according to phenotype characterization. The resistance susceptibility revealed 31 distinct profiles, with higher prevalence of streptomycin (61/62), nalidixic acid (50/62), tetracycline (43/62) and β-lactam drugs (37/62). blaCMY-2 was the more frequent β-lactamase gene found (38/62); other resistance genes found were blaCTX-M (2/62), blaSHV (3/62) and blaTEM-1 (38/62). No carbapenemase genes was found. The Pulsed-Field Gel Electrophoresis showed 58 different profiles. https://www.selleckchem.com/products/17-AAG(Geldanamycin).html Strains with a larger number of antimicrobial resistance were grouped into ten major clusters apart from others. The spread of resistance by ampC continues to rise, thereby turning concern to public health, since the β-lactam antimicrobials are used as a therapeutic treatment in humans.Oral pre-exposure prophylaxis (PrEP) for HIV-negative individuals at high risk was introduced in Lesotho in April 2016. To assess the feasibility and acceptability of PrEP in Lesotho and to study the attitudes and beliefs around HIV risk and prevention measures among young women, between September and December 2016 we asked 302 female university students at fourteen higher education institutions in Lesotho about their sexual behavior, experiences of sexual coercion and abuse, HIV risk perception, willingness to use PrEP, as well as their attitudes toward condom use and self-administration of daily medications. Overall, 57.3% of the sample reported perceiving themselves at risk of acquiring HIV and 32.1% reported being strongly willing to use PrEP if it were available in their community. In a multivariate mediation analysis, perceived HIV risk was associated with 11.5 percentage points increase in likelihood of using PrEP (p = 0.041). Multiple concurrent sexual partnership was associated with 16.1 percentage pd not report IPV in their network of peers (p = 0.009). These findings support the inclusion of individuals with multiple concurrent sexual partners among the key populations for PrEP provision and confirm that willingness to use PrEP is not solely driven by HIV risk perception. They also indicate that the presence of IPV in peer networks is related to one's willingness to use PrEP. PrEP service provision may generate synergies with IPV prevention programs when offered within this framework.
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  • This finding contributes to the understanding of the complex and multilayered regulation of ADAM17 at the cell surface. Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semiautomated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available. BACKGROUND Prophylactic inferior vena cava (IVC) filter use in bariatric surgery patients is a physician- and patient-dependent practice pattern with unclear safety and efficacy. Factors that mediate physicians' decisions for IVC filter placement preoperatively remain unclear. The role of race in decision-making also remains unclear. METHODS From the 2015-2016 MBASQIP database, patient characteristics leading to IVC filter use and outcomes after IVC filter placement were compared between Black and White primary bariatric surgery patients. RESULTS Prophylactic IVC filter was used in 0.66% of Black and White patients. IVC filter use was three-fold higher in Black patients, despite this cohort having a lower venous thromboembolism (VTE) risk profile than White counterparts. Black race was an independent predictor for IVC filter placement on multivariate analysis. After receiving an IVC filter, Black patients had higher rates of 30-day adverse outcomes. CONCLUSIONS In this study, Black race was independently associated with the likelihood of receiving a prophylactic IVC filter, despite lower rates of VTE risk factors and lack of recommendations for its use. Further research is needed to explore why this disparity in clinical practice exists. BACKGROUND Among melanoma patients with a tumor-positive sentinel node biopsy (SNB), approximately 20% harbor disease in non-sentinel nodes (nSN), as determined by a completion lymph node dissection (CLND). CLND lacks a survival benefit and has high morbidity. This study assesses predictive factors for nSN metastasis and validates five models predicting nSN metastasis. METHODS Patients with invasive melanoma were identified from the ** Cancer Agency (2005-2015). Clinicopathological data were collected from 296 patients who underwent a CLND after a positive SNB. Multivariate analysis was completed to assess predictive variables in the study population. Five models were externally validated using overall model performance (Brier score [calibration and discrimination]) and discrimination (area under the ROC curve [AUC]). RESULTS Seventy-three patients had nSN metastasis at the time of CLND. The variable most predictive of nSN involvement was lymphovascular invasion (odds ratio [OR] 3.99; 95% confidence interval [CI] 1.67-9.54; p = 0.002). The highest discrimination was Lee et al. (2004) (AUC 0.68 [95% CI 0.61-0.75]), Rossi et al. (2018) (AUC 0.68 [95% CI 0.57-0.77]), and Bertolli et al. (2019) (AUC 0.68 [95% CI 0.60-0.75]). Rossi et al. (2018) had the lowest overall model performance (Brier score 0.44). Rossi et al. (2018) and Bertolli et al. https://www.selleckchem.com/products/Azacitidine(Vidaza).html (2019) had the ability to stratify patients to a risk of nSN involvement up to 99% and 95%, respectively. CONCLUSION Bertolli et al. (2019) had amongst the highest overall model performance, was the most clinically meaningful and is recommended as the preferred model for predicting nSN metastasis. BACKGROUND As Canada's population ages, incidence of gastric cancer in elderly patients is increasing. There is little data on treatment and outcomes of gastric cancer in patients older than age 75. This study aimed to assess treatment patterns and outcomes of non-metastatic elderly gastric cancer patients in Alberta, Canada. METHODS Records of elderly patients (age 75 or older) diagnosed with localized gastric or gastroesophageal junction cancer between 2007 and 2012 who received curative intent surgery were retrospectively collected from the Alberta Cancer Registry. A chart review was completed to gather demographics; treatment details of surgery, chemotherapy, and radiotherapy; and outcomes. Descriptive analyses were undertaken, and variables were compared with parametric and nonparametric tests where appropriate. RESULTS 130 predominantly male (69%) patients, median age 80 (range 75-96) were included. 17 patients (13%) received multimodality therapy. 115 (88.5%) had negative margins on final pathology. Mean lymph nodes retrieved were 16 (range 0-43). 46 surgical patients (35.4%) had grade II or higher complications. 13 patients had a perioperative death (Clavien grade V). Four (3.1%) patients completed perioperative chemotherapy, and 13 (10%) patients had adjuvant chemo/radiotherapy. 50 (38.5%) recurred at median 13 months, while 80 (61.5%) did not have a recurrence of their cancer at any time during follow up. The 5 year DFS for the surgery only group was 67.3% and multimodality group was 52.9% (p = 0.25). The 5 year OS for the surgery only group was 38.9% and multimodality group was 47.1% (p = 0.52). CONCLUSIONS Our findings suggest that even with surgery alone, selected elderly patients with non-metastatic gastric cancer can obtain apparent prolonged survival, despite not receiving standard of care multimodality therapy. More studies are needed to optimise elderly patients' treatment selection. Mycoplasma contamination threatens both the safety of biologics produced in cell substrates as well as the quality of scientific results based on cell-culture observations. Methods currently used to detect contamination of cells include culture, enzymatic activity, immunofluorescence and PCR but suffer from some limitations. High throughput sequencing (HTS) can be used to identify microbes like mycoplasmas in biologics since it enables an unbiased approach to detection without the need to design specific primers to pre-amplify target sequences but it does not enable the confirmation of microbial infection since this could reflect carryover of inert sequences. In order to unambiguously differentiate the presence of live or dead mycoplasmas in biological products, the present method was developed based on metabolic RNA labelling of newly synthetized mycoplasmal RNAs. HTS of labelled RNA detected A549 cell infection with Acholeplasma laidlawii in a manner similar to both PCR and culture and demonstrated that this technique can unambiguously identify bacterial species and differentiates infected cells from cells exposed to a high inoculum of heat-inactivated mycoplasmas.
    This finding contributes to the understanding of the complex and multilayered regulation of ADAM17 at the cell surface. Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semiautomated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available. BACKGROUND Prophylactic inferior vena cava (IVC) filter use in bariatric surgery patients is a physician- and patient-dependent practice pattern with unclear safety and efficacy. Factors that mediate physicians' decisions for IVC filter placement preoperatively remain unclear. The role of race in decision-making also remains unclear. METHODS From the 2015-2016 MBASQIP database, patient characteristics leading to IVC filter use and outcomes after IVC filter placement were compared between Black and White primary bariatric surgery patients. RESULTS Prophylactic IVC filter was used in 0.66% of Black and White patients. IVC filter use was three-fold higher in Black patients, despite this cohort having a lower venous thromboembolism (VTE) risk profile than White counterparts. Black race was an independent predictor for IVC filter placement on multivariate analysis. After receiving an IVC filter, Black patients had higher rates of 30-day adverse outcomes. CONCLUSIONS In this study, Black race was independently associated with the likelihood of receiving a prophylactic IVC filter, despite lower rates of VTE risk factors and lack of recommendations for its use. Further research is needed to explore why this disparity in clinical practice exists. BACKGROUND Among melanoma patients with a tumor-positive sentinel node biopsy (SNB), approximately 20% harbor disease in non-sentinel nodes (nSN), as determined by a completion lymph node dissection (CLND). CLND lacks a survival benefit and has high morbidity. This study assesses predictive factors for nSN metastasis and validates five models predicting nSN metastasis. METHODS Patients with invasive melanoma were identified from the BC Cancer Agency (2005-2015). Clinicopathological data were collected from 296 patients who underwent a CLND after a positive SNB. Multivariate analysis was completed to assess predictive variables in the study population. Five models were externally validated using overall model performance (Brier score [calibration and discrimination]) and discrimination (area under the ROC curve [AUC]). RESULTS Seventy-three patients had nSN metastasis at the time of CLND. The variable most predictive of nSN involvement was lymphovascular invasion (odds ratio [OR] 3.99; 95% confidence interval [CI] 1.67-9.54; p = 0.002). The highest discrimination was Lee et al. (2004) (AUC 0.68 [95% CI 0.61-0.75]), Rossi et al. (2018) (AUC 0.68 [95% CI 0.57-0.77]), and Bertolli et al. (2019) (AUC 0.68 [95% CI 0.60-0.75]). Rossi et al. (2018) had the lowest overall model performance (Brier score 0.44). Rossi et al. (2018) and Bertolli et al. https://www.selleckchem.com/products/Azacitidine(Vidaza).html (2019) had the ability to stratify patients to a risk of nSN involvement up to 99% and 95%, respectively. CONCLUSION Bertolli et al. (2019) had amongst the highest overall model performance, was the most clinically meaningful and is recommended as the preferred model for predicting nSN metastasis. BACKGROUND As Canada's population ages, incidence of gastric cancer in elderly patients is increasing. There is little data on treatment and outcomes of gastric cancer in patients older than age 75. This study aimed to assess treatment patterns and outcomes of non-metastatic elderly gastric cancer patients in Alberta, Canada. METHODS Records of elderly patients (age 75 or older) diagnosed with localized gastric or gastroesophageal junction cancer between 2007 and 2012 who received curative intent surgery were retrospectively collected from the Alberta Cancer Registry. A chart review was completed to gather demographics; treatment details of surgery, chemotherapy, and radiotherapy; and outcomes. Descriptive analyses were undertaken, and variables were compared with parametric and nonparametric tests where appropriate. RESULTS 130 predominantly male (69%) patients, median age 80 (range 75-96) were included. 17 patients (13%) received multimodality therapy. 115 (88.5%) had negative margins on final pathology. Mean lymph nodes retrieved were 16 (range 0-43). 46 surgical patients (35.4%) had grade II or higher complications. 13 patients had a perioperative death (Clavien grade V). Four (3.1%) patients completed perioperative chemotherapy, and 13 (10%) patients had adjuvant chemo/radiotherapy. 50 (38.5%) recurred at median 13 months, while 80 (61.5%) did not have a recurrence of their cancer at any time during follow up. The 5 year DFS for the surgery only group was 67.3% and multimodality group was 52.9% (p = 0.25). The 5 year OS for the surgery only group was 38.9% and multimodality group was 47.1% (p = 0.52). CONCLUSIONS Our findings suggest that even with surgery alone, selected elderly patients with non-metastatic gastric cancer can obtain apparent prolonged survival, despite not receiving standard of care multimodality therapy. More studies are needed to optimise elderly patients' treatment selection. Mycoplasma contamination threatens both the safety of biologics produced in cell substrates as well as the quality of scientific results based on cell-culture observations. Methods currently used to detect contamination of cells include culture, enzymatic activity, immunofluorescence and PCR but suffer from some limitations. High throughput sequencing (HTS) can be used to identify microbes like mycoplasmas in biologics since it enables an unbiased approach to detection without the need to design specific primers to pre-amplify target sequences but it does not enable the confirmation of microbial infection since this could reflect carryover of inert sequences. In order to unambiguously differentiate the presence of live or dead mycoplasmas in biological products, the present method was developed based on metabolic RNA labelling of newly synthetized mycoplasmal RNAs. HTS of labelled RNA detected A549 cell infection with Acholeplasma laidlawii in a manner similar to both PCR and culture and demonstrated that this technique can unambiguously identify bacterial species and differentiates infected cells from cells exposed to a high inoculum of heat-inactivated mycoplasmas.
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  • Result also support the notion that orthorexia has two dimensions, healthy and nervosa, which are differently related to psychological factors, herein mindfulness. Level of evidence Level III, cohort study.Purpose Orthorexia Nervosa (ON) is defined as a pathological eating behaviour stemming from being "healthy" or "pure". Survey-based studies typically rely on the ORTO-15 questionnaire or its variations to detect orthorexia. However, frequent post-hoc adjustments to the ORTO-15 suggest psychometric problems. In this study, we explored people's cognitions about the ORTO-15 items to (1) identify problems specific to ORTO-15 items and (2) explore participants' understanding of ON symptoms. Methods Fifty adult participants (40% male, mean age = 34.0 ± 14.4 years) completed the ORTO-15, the Eating Attitudes Test (EAT-26) and the Obsessive-Compulsive Inventory-Revised edition (OCI-R). Qualitative data were collected using the modified "think aloud" protocol, which asked participants to 'verbalise' their responses to the ORTO-15 items. These qualitative responses were first analysed conjunctively with the quantitative responses; then subjected to thematic analysis. Results ORTO-15 identified 64% of the participants fidence V (cross-sectional descriptive study with qualitative analysis).We present the results of hydrodynamic simulations using the method of multi-particle collision dynamics for a system of squirmer microswimmers moving under the influence of gravity at low Reynolds numbers. In addition, the squirmers are bottom-heavy so that they experience a torque which aligns them along the vertical. https://www.selleckchem.com/products/ljh685.html The squirmers interact hydrodynamically by the flow fields of a stokeslet and rotlet, which are initiated by the acting gravitational force and torque, respectively, and by their own flow fields. By varying the ratio of swimming to bulk sedimentation velocity and the torque, we determine state diagrams for the emergent collective dynamics of neutral squirmers as well as strong pushers and pullers. For low swimming velocity and torque we observe conventional sedimentation, while the sedimentation profile becomes inverted when their values are increased. For neutral squirmers we discover convective rolls of circulating squirmers between both sedimentation states, which sit at the bottom of the system and are fed by plumes made of collectively sinking squirmers. At larger torques porous clusters occur that spawn single squirmers. The two latter states can also occur transiently starting from a uniform squirmer distribution and then disappear in the long-time limit. For strong pushers and pullers only weak plume formation is observed.Interactions between different pest control methods can affect Integrated Pest Management efficiency. This study sought to evaluate (1) if Si accumulation is related to the level of constitutive resistance in sorghum genotypes, (2) the level of Si induces resistance by antibiosis in sorghum genotypes with different levels of constitutive resistance to Schizaphis graminum (Rondani) (reared individualized or in colonies), and (3) the fitness of Lysiphlebus testaceipes (Cresson) in aphids reared on Si-treated and untreated plants. Several experiments were conducted under greenhouse conditions, using sorghum genotypes with different levels of resistance grown in pots with or without the addition of Si to the soil. The susceptible (BR007B), moderately resistant (GB3B), and highly resistant (TX430XGR111) genotypes all absorbed more Si when it was added to the soil compared with when it was not amended. However, the final Si content of treated plants was not related to the level of constitutive resistance among treated genotypes. While Si soil application did reduce the fecundity of individualized aphids reared on the susceptible and moderately resistant sorghum plants, it did not reduce populational growth of aphid colonies, independent of the level of plant's constitutive resistance. Parasitoid (L. testaceipes) had higher weight when reared from aphids fed on plants with added Si. Sorghum × constitutive resistance × S. graminum interactions were affected by plant Si content only for individualized aphids but not for aphid colonies. Sorghum × S. graminum × L. testaceipes interactions suggest that Si can have, overall, a positive effect on the biological control of S. graminum.Colonies of leaf-cutting ants of the genus Atta need to collect large quantities of vegetal substrate in their environment to ensure their growth. They do so by building and extending over time a foraging network that consists of several underground tunnels extending above ground by physical trails. This paper presents a longitudinal study of the foraging network of two mature colonies of the grass-cutting ant Atta capiguara (Gonçalves) located in a pasture in central Brazil. Specifically, we investigated whether the extension of the foraging area of the colonies required to reach new resources occurs by building new and longer underground tunnels or by building new and longer physical trails. Each nest was surveyed at intervals of approximately 15 days during 1 year. At each survey we mapped the position of the tunnel entrances and foraging trails at which activity was observed. In addition, we assessed the excavation effort of the colonies since the last survey by the number and distance to the nest of new tunnel entrances, and the physical trail construction effort by the number and length of newly built physical trails. Our study reveals that in A. capiguara the collection of new resources around the nest required to ensure the continuous growth of the colonies is achieved mainly through the excavation of new underground tunnels, opening at greater distance from the nest, not through the building of longer aboveground physical trails.The sugarcane hairy borer, Hyponeuma taltula (Schaus, 1904), attacks the base of sugarcane and causes the death of the apical bud, a symptom known as "dead heart." In recent years, there has been significant infestation in Brazilian sugarcane crops. With the purpose of finding methods for controlling and/or monitoring the pest for the sustainable cultivation of sugarcane, we characterized the mating behavior of H. taltula and confirmed the release of a sex pheromone by this insect. Sexual activity was observed between the second and ninth hour of scotophase, during which female calling caused the onset of male courtship behaviors and increased their frequency. An ethogram was built showing that males perform seven observable steps (1) wing flapping, (2) walking with wing flapping, (3) flying, (4) flying towards the female, (5) landing near the female and walking around her, (6) attempting copulation, and (7) copulation (mating). Female sex gland extracts also triggered attraction and male courtship behaviors.
    Result also support the notion that orthorexia has two dimensions, healthy and nervosa, which are differently related to psychological factors, herein mindfulness. Level of evidence Level III, cohort study.Purpose Orthorexia Nervosa (ON) is defined as a pathological eating behaviour stemming from being "healthy" or "pure". Survey-based studies typically rely on the ORTO-15 questionnaire or its variations to detect orthorexia. However, frequent post-hoc adjustments to the ORTO-15 suggest psychometric problems. In this study, we explored people's cognitions about the ORTO-15 items to (1) identify problems specific to ORTO-15 items and (2) explore participants' understanding of ON symptoms. Methods Fifty adult participants (40% male, mean age = 34.0 ± 14.4 years) completed the ORTO-15, the Eating Attitudes Test (EAT-26) and the Obsessive-Compulsive Inventory-Revised edition (OCI-R). Qualitative data were collected using the modified "think aloud" protocol, which asked participants to 'verbalise' their responses to the ORTO-15 items. These qualitative responses were first analysed conjunctively with the quantitative responses; then subjected to thematic analysis. Results ORTO-15 identified 64% of the participants fidence V (cross-sectional descriptive study with qualitative analysis).We present the results of hydrodynamic simulations using the method of multi-particle collision dynamics for a system of squirmer microswimmers moving under the influence of gravity at low Reynolds numbers. In addition, the squirmers are bottom-heavy so that they experience a torque which aligns them along the vertical. https://www.selleckchem.com/products/ljh685.html The squirmers interact hydrodynamically by the flow fields of a stokeslet and rotlet, which are initiated by the acting gravitational force and torque, respectively, and by their own flow fields. By varying the ratio of swimming to bulk sedimentation velocity and the torque, we determine state diagrams for the emergent collective dynamics of neutral squirmers as well as strong pushers and pullers. For low swimming velocity and torque we observe conventional sedimentation, while the sedimentation profile becomes inverted when their values are increased. For neutral squirmers we discover convective rolls of circulating squirmers between both sedimentation states, which sit at the bottom of the system and are fed by plumes made of collectively sinking squirmers. At larger torques porous clusters occur that spawn single squirmers. The two latter states can also occur transiently starting from a uniform squirmer distribution and then disappear in the long-time limit. For strong pushers and pullers only weak plume formation is observed.Interactions between different pest control methods can affect Integrated Pest Management efficiency. This study sought to evaluate (1) if Si accumulation is related to the level of constitutive resistance in sorghum genotypes, (2) the level of Si induces resistance by antibiosis in sorghum genotypes with different levels of constitutive resistance to Schizaphis graminum (Rondani) (reared individualized or in colonies), and (3) the fitness of Lysiphlebus testaceipes (Cresson) in aphids reared on Si-treated and untreated plants. Several experiments were conducted under greenhouse conditions, using sorghum genotypes with different levels of resistance grown in pots with or without the addition of Si to the soil. The susceptible (BR007B), moderately resistant (GB3B), and highly resistant (TX430XGR111) genotypes all absorbed more Si when it was added to the soil compared with when it was not amended. However, the final Si content of treated plants was not related to the level of constitutive resistance among treated genotypes. While Si soil application did reduce the fecundity of individualized aphids reared on the susceptible and moderately resistant sorghum plants, it did not reduce populational growth of aphid colonies, independent of the level of plant's constitutive resistance. Parasitoid (L. testaceipes) had higher weight when reared from aphids fed on plants with added Si. Sorghum × constitutive resistance × S. graminum interactions were affected by plant Si content only for individualized aphids but not for aphid colonies. Sorghum × S. graminum × L. testaceipes interactions suggest that Si can have, overall, a positive effect on the biological control of S. graminum.Colonies of leaf-cutting ants of the genus Atta need to collect large quantities of vegetal substrate in their environment to ensure their growth. They do so by building and extending over time a foraging network that consists of several underground tunnels extending above ground by physical trails. This paper presents a longitudinal study of the foraging network of two mature colonies of the grass-cutting ant Atta capiguara (Gonçalves) located in a pasture in central Brazil. Specifically, we investigated whether the extension of the foraging area of the colonies required to reach new resources occurs by building new and longer underground tunnels or by building new and longer physical trails. Each nest was surveyed at intervals of approximately 15 days during 1 year. At each survey we mapped the position of the tunnel entrances and foraging trails at which activity was observed. In addition, we assessed the excavation effort of the colonies since the last survey by the number and distance to the nest of new tunnel entrances, and the physical trail construction effort by the number and length of newly built physical trails. Our study reveals that in A. capiguara the collection of new resources around the nest required to ensure the continuous growth of the colonies is achieved mainly through the excavation of new underground tunnels, opening at greater distance from the nest, not through the building of longer aboveground physical trails.The sugarcane hairy borer, Hyponeuma taltula (Schaus, 1904), attacks the base of sugarcane and causes the death of the apical bud, a symptom known as "dead heart." In recent years, there has been significant infestation in Brazilian sugarcane crops. With the purpose of finding methods for controlling and/or monitoring the pest for the sustainable cultivation of sugarcane, we characterized the mating behavior of H. taltula and confirmed the release of a sex pheromone by this insect. Sexual activity was observed between the second and ninth hour of scotophase, during which female calling caused the onset of male courtship behaviors and increased their frequency. An ethogram was built showing that males perform seven observable steps (1) wing flapping, (2) walking with wing flapping, (3) flying, (4) flying towards the female, (5) landing near the female and walking around her, (6) attempting copulation, and (7) copulation (mating). Female sex gland extracts also triggered attraction and male courtship behaviors.
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  • BACKGROUND Falls and fall-related injuries are a foremost health concern among older adults aged 60 years and above. Fall-risk-increasing drugs (FRIDs) use by older adults is one related cause of falling, and it is frequently used among older adults. Pharmacist-led counselling is an aspect of patient education that has been associated with improved therapeutic outcome and quality of life in high income countries with scarcity of information in low-middle income countries. This study therefore aims to assess hospital pharmacists' knowledge and counselling on fall-related medications using the list compiled by the Swedish National Board of Health and Welfare on FRIDs and orthostatic drugs (ODs). METHODS A cross-sectional survey was carried out among 56 pharmacists working in a teaching hospital in Nigeria, between July and August 2019, using a self-administered questionnaire. Data were summarized with descriptive statistics while chi-square test was used for categorical variables at p  less then  0.05. RESULTS s and ODs was noted among the hospital pharmacists. However, engagement of pharmacists on counsel that focus on medication use, adverse effect and storage was relatively better. Thus, there is a general need to create awareness about fall-risk-increasing drugs among hospital pharmacists, so as to help improve the therapeutic outcome particularly in the older adults.BACKGROUND In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether-lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency. METHODS Here, an amplicon sequencing approach was used to identify mutations in the Pfk13 gene in eighty-one P. falciparum isolates collected from three different regions of Senegal. RESULTS In total, 10 SNPs around the propeller domain were identified; one synonymous SNP and nine non-synonymous SNPs, and two insertions. https://www.selleckchem.com/products/dual-specificity-protein-phosphatase-1-6-Inhibitor-bcl.html Three of these SNPs (T478T, A578S and V637I) were located in the propeller domain. A578S, is the most frequent mutation observed in Africa, but has not previously been reported in Senegal. A previous study has suggested that A578S could disrupt the function of the Pfk13 propeller region. CONCLUSION As the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia, further studies are necessary to assess the new SNPs reported in this study.BACKGROUND Particulate matter (PM) can cause various negative acute and chronic diseases of the respiratory system, including the upper airways. Curcumin has been reported to have anti-inflammatory and anti-oxidative effects; therefore, we investigated the effects of curcumin on nasal fibroblasts exposed to urban PM (UPM). METHODS Samples of inferior turbinate tissue were obtained from six patients. Flow cytometry was used to assess the levels of reactive oxygen species (ROS) following the treatment of nasal fibroblasts with UPM and/or curcumin. We evaluated the effects of UPM and/or curcumin on the expression of phosphorylated ERK, Nrf2, HO-1, and SOD2 in fibroblasts by Western blotting. RESULTS When UPM was applied to nasal fibroblasts, ROS production was significantly increased in a dose-dependent manner. UPM-exposed fibroblasts caused the activation of ERK to increase HO-1 expression and decrease SOD2 expression. Treatment with curcumin reduced the UPM-mediated increase in ROS; this decrease in ROS occurred in a dose-dependent manner. The UPM-induced activation of ERK was inhibited by curcumin. Nrf2 production was also promoted to increase the expression of HO-1 and SOD2 by curcumin. CONCLUSION Curcumin reduced ROS production caused by UPM in human nasal fibroblasts in a dose-dependent manner, suggesting that curcumin has anti-oxidative effects and may be useful in the treatment of nasal diseases caused by UPM, such as allergic and chronic rhinitis.BACKGROUND All around the world, the paralegal program prepares members of marginalized communities to face the legal system. Having a common background with their clients and being capable of conducting flexible work, paralegals' role moves beyond enlarging the beneficiaries of legal aid to addressing intersectional issues around health-related rights. This study assesses the health and other impacts of paralegals recruited by Lembaga Bantuan Hukum Masyarakat (LBHM), a human rights organization which provides legal assistance and operates in Jakarta, Indonesia. The positive results these paralegals can bring in the specific context can contribute to the development of community-based paralegals elsewhere. METHODS This mixed methods research was carried out in 2016-2018. In 2016, a quantitative survey was administered to LBHM-trained paralegals and a sub-set of paralegals who completed the survey were then also interviewed. Quantitative data were analysed using SPSS, and, for the qualitative data, thematic anients and lawyers to champions of the health-related rights of their clients can happen as a result of adequate training, support, and networks with other agents in criminal justice system.BACKGROUND Foodborne pathogens and their biofilms are considered as one of the most serious problems in human health and food industry. Moreover, safety of foods is a main global concern because of the increasing use of chemical food additives. Ensuring food safety enhances interest in discovery of new alternative compounds such as antimicrobial peptides (AMPs), which can be used as bio-preservatives in the food industry. In this study, the most important antimicrobial peptides of camel milk lactoferrin (lactoferrampin and lactoferricin) were recombinantly expressed in the form of chimeric peptide (cLFchimera) in a food-grade L. lactis strain. P170 expression system was used to express secreted cLFchimera using pAMJ1653 expression vector which harbors a safe (non-antibiotic) selectable marker. RESULTS Peptide purification was carried out using Ni-NTA agarose column from culture medium with concentration of 0.13 mg/mL. The results of disk diffusion test revealed that cLFchimera had considerable antimicrobial activity against a number of major foodborne bacteria.
    BACKGROUND Falls and fall-related injuries are a foremost health concern among older adults aged 60 years and above. Fall-risk-increasing drugs (FRIDs) use by older adults is one related cause of falling, and it is frequently used among older adults. Pharmacist-led counselling is an aspect of patient education that has been associated with improved therapeutic outcome and quality of life in high income countries with scarcity of information in low-middle income countries. This study therefore aims to assess hospital pharmacists' knowledge and counselling on fall-related medications using the list compiled by the Swedish National Board of Health and Welfare on FRIDs and orthostatic drugs (ODs). METHODS A cross-sectional survey was carried out among 56 pharmacists working in a teaching hospital in Nigeria, between July and August 2019, using a self-administered questionnaire. Data were summarized with descriptive statistics while chi-square test was used for categorical variables at p  less then  0.05. RESULTS s and ODs was noted among the hospital pharmacists. However, engagement of pharmacists on counsel that focus on medication use, adverse effect and storage was relatively better. Thus, there is a general need to create awareness about fall-risk-increasing drugs among hospital pharmacists, so as to help improve the therapeutic outcome particularly in the older adults.BACKGROUND In 2006, the Senegalese National Malaria Control Programme recommended artemisinin-based combination therapy (ACT) with artemether-lumefantrine as the first-line treatment for uncomplicated Plasmodium falciparum malaria. To date, multiple mutations associated with artemisinin delayed parasite clearance have been described in Southeast Asia in the Pfk13 gene, such as Y493H, R539T, I543T and C580Y. Even though ACT remains clinically and parasitologically efficacious in Senegal, the spread of resistance is possible as shown by the earlier emergence of resistance to chloroquine in Southeast Asia that subsequently spread to Africa. Therefore, surveillance of artemisinin resistance in malaria endemic regions is crucial and requires the implementation of sensitive tools, such as next-generation sequencing (NGS) which can detect novel mutations at low frequency. METHODS Here, an amplicon sequencing approach was used to identify mutations in the Pfk13 gene in eighty-one P. falciparum isolates collected from three different regions of Senegal. RESULTS In total, 10 SNPs around the propeller domain were identified; one synonymous SNP and nine non-synonymous SNPs, and two insertions. https://www.selleckchem.com/products/dual-specificity-protein-phosphatase-1-6-Inhibitor-bcl.html Three of these SNPs (T478T, A578S and V637I) were located in the propeller domain. A578S, is the most frequent mutation observed in Africa, but has not previously been reported in Senegal. A previous study has suggested that A578S could disrupt the function of the Pfk13 propeller region. CONCLUSION As the genetic basis of possible artemisinin resistance may be distinct in Africa and Southeast Asia, further studies are necessary to assess the new SNPs reported in this study.BACKGROUND Particulate matter (PM) can cause various negative acute and chronic diseases of the respiratory system, including the upper airways. Curcumin has been reported to have anti-inflammatory and anti-oxidative effects; therefore, we investigated the effects of curcumin on nasal fibroblasts exposed to urban PM (UPM). METHODS Samples of inferior turbinate tissue were obtained from six patients. Flow cytometry was used to assess the levels of reactive oxygen species (ROS) following the treatment of nasal fibroblasts with UPM and/or curcumin. We evaluated the effects of UPM and/or curcumin on the expression of phosphorylated ERK, Nrf2, HO-1, and SOD2 in fibroblasts by Western blotting. RESULTS When UPM was applied to nasal fibroblasts, ROS production was significantly increased in a dose-dependent manner. UPM-exposed fibroblasts caused the activation of ERK to increase HO-1 expression and decrease SOD2 expression. Treatment with curcumin reduced the UPM-mediated increase in ROS; this decrease in ROS occurred in a dose-dependent manner. The UPM-induced activation of ERK was inhibited by curcumin. Nrf2 production was also promoted to increase the expression of HO-1 and SOD2 by curcumin. CONCLUSION Curcumin reduced ROS production caused by UPM in human nasal fibroblasts in a dose-dependent manner, suggesting that curcumin has anti-oxidative effects and may be useful in the treatment of nasal diseases caused by UPM, such as allergic and chronic rhinitis.BACKGROUND All around the world, the paralegal program prepares members of marginalized communities to face the legal system. Having a common background with their clients and being capable of conducting flexible work, paralegals' role moves beyond enlarging the beneficiaries of legal aid to addressing intersectional issues around health-related rights. This study assesses the health and other impacts of paralegals recruited by Lembaga Bantuan Hukum Masyarakat (LBHM), a human rights organization which provides legal assistance and operates in Jakarta, Indonesia. The positive results these paralegals can bring in the specific context can contribute to the development of community-based paralegals elsewhere. METHODS This mixed methods research was carried out in 2016-2018. In 2016, a quantitative survey was administered to LBHM-trained paralegals and a sub-set of paralegals who completed the survey were then also interviewed. Quantitative data were analysed using SPSS, and, for the qualitative data, thematic anients and lawyers to champions of the health-related rights of their clients can happen as a result of adequate training, support, and networks with other agents in criminal justice system.BACKGROUND Foodborne pathogens and their biofilms are considered as one of the most serious problems in human health and food industry. Moreover, safety of foods is a main global concern because of the increasing use of chemical food additives. Ensuring food safety enhances interest in discovery of new alternative compounds such as antimicrobial peptides (AMPs), which can be used as bio-preservatives in the food industry. In this study, the most important antimicrobial peptides of camel milk lactoferrin (lactoferrampin and lactoferricin) were recombinantly expressed in the form of chimeric peptide (cLFchimera) in a food-grade L. lactis strain. P170 expression system was used to express secreted cLFchimera using pAMJ1653 expression vector which harbors a safe (non-antibiotic) selectable marker. RESULTS Peptide purification was carried out using Ni-NTA agarose column from culture medium with concentration of 0.13 mg/mL. The results of disk diffusion test revealed that cLFchimera had considerable antimicrobial activity against a number of major foodborne bacteria.
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